Organic Chemistry International

Volume 2014 (2014), Article ID 761209, 5 pages

http://dx.doi.org/10.1155/2014/761209

Research Article

An Efficient One-Pot Multi-Component Synthesis of 3,4-Dihydropyrimidin-2-(1H)-Ones/Thiones Catalyzed by Bismuth (III) Sulfate Trihydrate under Solvent-Free Conditions

Farhad Hatamjafari

Department of Chemistry, Faculty of Science, Islamic Azad University, Tonekabon Branch, Tonekabon, Iran

Received 17 October 2013; Revised 8 January 2014; Accepted 8 January 2014; Published 13 March 2014

Academic Editor: Ashraf Aly Shehata

Copyright © 2014 Farhad Hatamjafari. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

A convenient and efficient protocol for the one-pot synthesis of 3,4-dihydropyrimidin-2-(1H)-one/thione derivatives of aldehydes, and 1,3-dicarbonyl compounds with Bismuth (III) sulfate trihydrate as the catalyst was described. We had the advantages of good performance, simplicity, and short time reaction under solvent-free conditions. The catalyst can be repeatedly reused without loss of its activity.

1. Introduction

Multi-component reactions play an important role in pharmaceutical industries. Pharmacies are trying to develop green chemistry reactions. Solvent-free synthesis of complex organic structures as drugs is the dream of every pharmacy. Multi-component reaction as a powerful tool for the rapid introduction of molecular diversity is evident and developed for the generation of heterocycles which receive growing interest [1–3]. Biginelli reaction is one of the most important multi-component reactions for the synthesis of dihydropyrimidinones/thiones. 3,4-Dihydropyrimidin-2(1H)-ones/thiones (DHPMs) reported the activity of many drugs as having antiviral, antibacterial, and antihypertensive effects, as calcium channel modulators [4–7], and as multidrug resistance reversal [8, 9]. Biological activity of some alkaloids isolated recently to 3,4 dihydropyrimidin-2(1H)-ones/thiones moiety [10, 11]. It was first synthesized by Biginelli in 1893 DHPMs as a pot condensation of an aldehyde, diketone, and urea under acidic conditions. These method has low yields, especially in the cases of some substituted aldehydes. To increase the efficiency of the reaction, Biginelli, various catalysts have been used [12].

Biginelli reaction suffers from low yields (20–50%) of products. Thus, in recent years, several methods to improve the use of Al(NO₃)₃·9H₂O [13], ZrCl₄ [14], zeolites [15], silica sulfuric acid [16], BF₃·OEt₂ [17], CuCl₂·2H₂O [18], SbCl₃ [19], RuCl₃ [20], natural catalyst [21], and glutamic acid [22] have been reported in the literature. However, some of these methods are expensive and harmful to the environment; stoichiometrically, the amount of catalyst, low yields, and incompatibility with other functional groups including product isolation methods is difficult. Therefore, there is still a need for a simple and efficient method for the synthesis of a pot dihydropyrimidinone and thiones under mild conditions. In recent years, eco-friendly industrial application, using green and reusable catalyst, has been studied.

Thus, green chemistry has been defined as a set of principles that reduces or eliminates the use or generation of hazardous chemical materials. It is as part of our current studies on the development of new routes in heterocyclic synthesis [22].

Herein, we want to use the Bismuth (III) sulfate trihydrate as a catalyst in a pot, three-component Biginelli reaction in solvent-free conditions between benzaldehyde, ethyl acetoacetate, and urea for synthesis of DHPMs. This approach (Scheme 1) for simple pot Biginelli was a remarkable performance (>86) of dihydropyrimidinones/thiones in a shorter reaction time (60–360 min) versus the reaction time required for other catalysts (Scheme 1).

Scheme 1: Synthesis of 3,4-dihydropyrimidinones/thiones derivatives.

2. Experimental

All chemicals were obtained from Merck or Fluka. Melting points were measured on an Electrothermal 9100 apparatus. Silica gel SILG/UV 254 plates were used for TLC. IR spectra were measured on a Shimadzu IR-470 Spectrophotometer. ¹H NMR and ¹³C NMR spectra were determined on Bruker 500 DRX AVANCE instrument at 500 and 125 MHz, respectively. The element analyses (C, H, N) were obtained from a Carlo ERBA Model EA 1108 analyzer carried out on Perkin Elmer 240c analyzer.

2.1. General Procedure for the Preparation of 3,4-Dihydropyrimidinones/Thiones (5a–m)

A mixture of aldehyde (2 mmol), ethyl acetoacetate (2.5 mmol), urea/thiourea (2.5 mmol), and Bismuth (III) sulfate trihydrate (10 mol%) was heated with stirring for 60 min in 90°C. After cooling, the reaction mixture was poured into crushed ice with stirring. The crude product was filtered, washed with cold water, dried, and recrystallized from 95 ethanol or ethyl acetate to give pure products (5a–m) (80–95). All compounds were fully characterized by elemental analysis, M.P., IR, CHN, and ¹H NMR and ¹³C NMR spectroscopy. The structures of all synthesized compounds (5a–m) have been depicted in Scheme 1.

2.2. Selected Spectra

5-(Ethoxycarbonyl)-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5a). White crystals, m.p. 206–208°C. IR (KBr, cm⁻¹): 3245, 1725, 1635. ¹H NMR (CDCl₃  δ ppm): 1.10 (t, 3H, , OCH₂CH₃), 2.24 (s, 3H, CH₃), 3.95 (q, 2H, .2 Hz, OCH₂), 5.10 (d, 1H, –CH), 7.28 (m, 5H, Ar–H), 7.77 (s, 1H, NH), 9.0 (s, 1H, NH). ¹³C NMR (CDCl₃  δ   ppm): 15.15, 19.00, 55.22, 59.95, 101.02, 112.22, 114.15, 126.33, 126.98, 128.45, 132.12, 149.16, 156.77, 164.11. Anal. Calcd for C₁₄H₁₆N₂O₃ (%): C, 64.62; H, 6.15; N, 10.72. Found: C, 64.58; H, 6.13; N, 10.72.

5-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5b). White crystals, m.p. 201–202°C. IR (KBr, cm⁻¹): 3240, 1730, 1635. ¹H NMR (CDCl₃  δ   ppm): 1.18 (t, 3H, , OCH₂ CH₃), 2.43 (s, 3H, CH₃), 3.91 (s, 3H, –O CH₃), 4.12 (q, 2H, , OCH₂ CH₃), 5.54 (d, 1H, –CH), 6.98 (d, 2H, , Ar–H), 7.24 (d, 2H, , Ar–H), 7.75 (s, 1H, NH), 9.33 (s, 1H, NH). ¹³C NMR (CDCl₃  δ   ppm): 14.55, 18.22, 56.11, 56.40, 61.10, 100.23, 116.83, 129.38, 138.54, 147.98, 158.09, 159.55, 165.43. Anal. Calcd for C₁₅H₁₈N₂O₄ (%): C, 62.06; H, 6.25; N, 9.65. Found: C, 62.04; H, 6.28; N, 9.67.

5-(Ethoxycarbonyl)-4-(4-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5c). White crystals m.p. 211–213°C. IR (KBr, cm⁻¹): 3240, 1735, 1625. ¹H NMR (CDCl₃  δ   ppm): 1.14 (t, 3H, J 7.02 Hz, OCH₂ CH₃), 2.35 (s, 3H, CH₃), 4.14 (q, 2H, , OCH₂ CH₃), 6.09 (d, 1H, , –CH), 7.78 (d, 2H, , Ar–H), 7.89 (s, 1H, NH), 8.25 (d, 2H, , Ar–H), 9.12 (s, 1H, NH). ¹³C NMR (CDCl₃  δ   ppm): 15.02, 19.11, 56.31, 60.75, 100.90, 120.18, 130.77, 139.55, 154.76, 155.79, 158.95, 166.44. Anal. Calcd for C₁₄H₁₅N₃O₅ (%): C, 55.06; H, 4.92; N, 13.74. Found: C, 55.12; H, 4.95; N, 13.68.

5-(Ethoxycarbonyl)-4-(4-chlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5d). White crystals, m.p. 215–216°C. IR (KBr, cm⁻¹): 3230, 1725, 1615. ¹H NMR (CDCl₃  δ   ppm): 1.16 (t, 3H, .09 Hz, OCH₂ CH₃), 2.44 (s, 3H, CH₃), 4.12 (q, 2H, .09 Hz, OCH₂ CH₃), 5.79 (d, 1H, 7, –CH), 7.24 (d, 2H, , Ar–H), 7.79 (s, 1H, NH), 7.84 (d, 2H, , Ar–H), 9.20 (s, 1H, NH). ¹³C NMR (CDCl₃  δ ppm): 14.58, 18.72, 56.46, 61.32, 101.92, 119.77, 131.59, 143.57, 154.26, 155.67, 159.98, 165.65. Anal. Calcd for C₁₄H₁₅ClN₂O₃ (%): C, 57.12; H, 5.08; N, 9.55. Found: C, 57.08; H, 5.06; N, 9.56.

5-(Ethoxycarbonyl)-4-(3-chlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5e). White crystals, m.p. 192-193°C. IR (KBr, cm⁻¹): 3235, 1725, 1630. ¹H NMR (CDCl₃  δ   ppm): 1.11 (t, 3H,  Hz, OCH₂ CH₃), 2.30 (s, 3H, CH₃), 4.01 (q, 2H, , OCH₂ CH₃), 5.96 (d, 1H, , –CH), 7.22–7.55 (m, 4H, Ar–H), 7.66 (s, 1H, NH), 9.18 (s, 1H, NH). ¹³C NMR (CDCl₃  δ   ppm): 14.65, 19.04, 56.33, 60.67, 100.89, 125.31, 128.35, 128.98, 129.83, 136.67, 143.64, 154.78, 159.57, 165.25. Anal. Calcd for C₁₄H₁₅ClN₂O₃ (%): C, 57.14; H, 5.10; N, 9.50. Found: C, 57.13; H, 5.08; N, 9.48.

5-(Ethoxycarbonyl)-4-(4-flurophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5f). White crystals, m.p. 182–184°C. IR (KBr, cm⁻¹): 3255, 1740, 1650. ¹H NMR (CDCl₃  δ     ppm): 1.18 (t, 3H, , OCH₂ CH₃), 2.39 (s, 3H, CH₃), 4.10 (q, 2H, , OCH₂ CH₃), 6.13 (d, 1H, , –CH), 7.55 (s, 1H, NH), 7.78 (d, 2H, , Ar–H), 7.95 (d, 2H, , Ar–H), 9.21 (s, 1H, NH). ¹³C NMR (CDCl₃δ ppm): 14.63, 18.98, 56.44, 61.35, 101.89, 122.78, 135.66, 148.08, 155.37, 158.67, 159.65, 165.90. Anal. Calcd for C₁₄H₁₅FN₂O₃ (%): C, 60.43; H, 5.39; N, 10.07. Found: C, 60.39; H, 5.36; N, 10.08.

5-(Ethoxycarbonyl)-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (5g). Yellow crystals, m.p. 208–210°C. IR (KBr, cm⁻¹): 3235, 1715, 1645, 1585, 1525. ¹H NMR (CDCl₃  δ   ppm): 1.12 (t, 3H, , OCH₂ CH₃), 2.31 (s, 3H, CH₃), 4.18 (q, 2H, , OCH₂), 5.23 (d, 1H, –CH), 7.38 (m, 5H, Ar–H), 7.75 (s, 1H, NH), 9.11 (s, 1H, NH). ¹³C NMR (CDCl₃  δ   ppm): 14.66, 18.67, 56.87, 60.76, 100.25, 112.75, 118.39, 125.08, 128.22, 130.14, 133.61, 153.86, 163.42, 181.48. Anal. Calcd for C₁₄H₁₆N₂O₂S (%): C, 60.85; H, 5.84; N, 10.14; S, 11.60. Found: C, 60.66; H, 5.86; N, 10.14; S, 11.66.

5-(Ethoxycarbonyl)-4-(3-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (5h). Yellow crystals, m.p. 205–207°C. IR (KBr, cm⁻¹): 3260, 1740, 1635, 1580, 1545. ¹H NMR (CDCl₃  δ   ppm): 1.15 (t, 3H, , OCH₂ CH₃), 2.33 (s, 3H, CH₃), 4.22 (q, 2H, , O CH₂ CH₃), 5.75 (d, 1H, , –CH), 7.24–7.46 (m, 4H, Ar–H), 7.88 (s, 1H, NH), 9.45 (s, 1H, NH). ¹³C NMR (CDCl₃  δ   ppm): 14.66, 19.12, 58.12, 60.68, 101.71, 127.45, 128.82, 129.55, 132.39, 135.28, 145.83, 161.02, 165.58, 180.29. Anal. Calcd for C₁₄H₁₅N₃O₄S (%): C, 52.33; H, 4.67; N, 13.08; S, 9.97. Found: C, 52.30; H, 4.66; N, 13.09; S, 9.98.

5-(Ethoxycarbonyl)-4-(4–methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (5i). Yellow crystals, m.p. 153–155°C. IR (KBr, cm⁻¹): 3235, 1720, 1630, 1570, 1535. ¹H NMR (CDCl₃) δ: 1.18 (t, 3H, , OCH₂ CH₃), 2.44 (s, 3H, CH₃), 4.23 (s, 3H, –O CH₃), 4.38 (q, 2H, , OCH₂ CH₃), 5.84 (d, 1H, –CH), 7.31 (d, 2H, , Ar–H), 7.42 (d, 2H, , Ar–H), 7.56 (s, 1H, NH), 9.21 (s, 1H, NH). ¹³C NMR (CDCl₃) δ: 14.87, 19.15, 56.25, 56.49, 60.78, 100.32, 115.65, 128.86, 138.28, 145.84, 160.35, 163.47, 181.66. Anal. Calcd for C₁₅H₁₈N₂O₃S (%): C, 58.82; H, 5.88; N, 9.15; S, 10.45. Found: C, 58.78; H, 5.86; N, 9.16; S, 10.44.

5-(Ethoxycarbonyl)-4-(2-chlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (5j). Yellow crystals, m.p. 218–220°C. IR (KBr, cm⁻¹): 3430, 3340, 1710, 1668, 1358, 1276. ¹H NMR (CDCl₃  δ   ppm): 1.03 (t, , 3H, CH₃), 2.11 (s, 3H,CH₃), 4.20 (q, , 4.28 Hz, 2H, CH₂O), 5.20 (s, 1H, CH), 6.90–7.25 (m, 4H, Ar–H), 8.41 (s, 1H, NH), 9.51 (s, 1H, NH). ¹³C NMR (CDCl₃  δ ppm): 14.52, 57.66, 61.05, 103.27, 125.55, 127.34, 128.62, 131.44, 132.53, 144.22, 160.11, 163.26, 177.43. Anal. Calcd for C₁₄H₁₅ClN₂O₂S (%): C, 54.19; H, 4.84; N, 9.03; S, 10.32. Found: C, 54.14; H, 4.77; N, 9.10; S, 10.25.

5-(Ethoxycarbonyl)-4-(2–nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (5k). Yellow crystals, m.p. 190–192°C. IR (KBr, cm⁻¹): 3338, 3289, 2996, 1685, 1572, 1355, 1310. ¹H NMR (CDCl₃  δ   ppm): 1.14 (t, , 3H, CH₃), 1.98 (s, 3 H, CH₃), 4.15 (q, , 4.55 Hz, 2H, CH₂O), 5.15 (s, 1H, CH), 6.8–7.38 (m, 4H, Ar–H): 7.22 (s, 1H, NH), 9.35 (s, 1H, NH). ¹³C NMR (CDCl₃  δ   ppm): 18.37, 56.36, 60.44, 101.48, 123.21, 125.72, 126.52, 130.26, 130.83, 142.77, 159.61, 161.12, 175.87. Anal. Calcd for C₁₄H₁₅N₃O₄S (%): C, 52.33; H, 4.67; N, 13.08; S, 9.97. Found: C, 52.26; H, 4.65; N, 13.12; S, 9.96.

5-(Ethoxycarbonyl)-4-(3–methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (5m). Yellow crystals, m.p. 160–162°C. IR (KBr, cm⁻¹): 3427, 3287, 2967, 1709, 1613, 1300, 1291. ¹H NMR (CDCl₃  δ   ppm): 1.22 (t, , 3H, CH₃), 2.30 (s, 3H, CH₃), 3.86 (s, 3H, Ar–OCH₃), 4.14 (q, , 4.1 Hz, 2H, CH₂O), 5.18 (s, 1H, CH), 6.8 (s, 1H, NH), 6.82–7.84 (m, 4H, Ar–H), 9.42 (s, 1H, NH). ¹³C NMR (CDCl₃  δ   ppm): 15.43, 19.62, 56.35, 56.78, 61.44, 100.02, 112.73, 126.11, 135.56, 147.67, 161.48, 164.29, 179.37. Anal. Calcd for C₁₅H₁₈N₂O₃S (%): C, 58.82; H, 5.88; N, 9.15; S, 10.45. Found: C, 58.77; H, 5.84; N, 9.16; S, 10.42.

3. Results and Discussion

Bismuth (III) sulfate trihydrate and other salts of Bismuth can be used as a catalyst in the synthesis of organic compounds considered [23–28]. The features of this catalyst could be of high interest because easily separated, environmentally friendly, reusable, clean and affordable. Dihydropyrimidines show a wide range of biological activities. We are interested to develop a simple method for the synthesis of Biginelli reaction DHPMs. Our own study of one-pot three-component Biginelli condensation using Bismuth (III) sulfate trihydrate as a catalyst (Scheme 1) and the reaction with benzaldehyde, ethyl acetoacetate, and urea to afford the product DHPMs as a model reaction (5a) has begun. Synthesis reaction mixture as a model (5a) to determine the appropriate response in the presence of various amounts of Bismuth (III) sulfate trihydrate catalyst under solvent-free conditions (Table 1) was selected. It was found that the yield of compound 5a was strongly affected by the catalyst amount. The best results under solvent-free conditions (entry 9) in the presence of 10 mol% catalyst (Table 1) were obtained. In various solvents such as ethanol, methanol, acetonitrile, dichloromethane and chloroform, ethyl acetate, THF, and under solvent-free conditions in the presence of 10 mol% the catalyst (Table 1) was examined. The best results were obtained in solvent-free conditions at the top and the shortest reaction time (entry 9).

Table 1: Bismuth (III) sulfate trihydrate catalyzed synthesis of 5-(ethoxycarbonyl)-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5a) in different solvents conditions.

Entry
Solvent
Catalyst (mol%)
Time (min)
Yield (%)

1
Ethanol
10
120
25

2
Methanol
10
120
25

3
Acetonitrile
10
120
40

4
Dichloromethane
10
120
33

5
Chloroform
10
120
35

6
Ethyl acetate
10
120
45

7
THF
10
120
20

8
Solvent-free
5
120
65

9
Solvent-free
10
60
89

10
Solvent-free
15
120
78

11
Solvent-free
20
120
55

12
Solvent-free
0
360
10

Reaction conditions: 2 mmol benzaldehyde, 2.5 mmol ethyl acetoacetate, 2.5 mmol urea/thiourea, and Bismuth (III) sulfate trihydrate (10 mol%) were refluxed with stirring for 60 min.

We were successful; 4-dihydropyrimidin-2(1H)-one/thione derivatives of aldehydes and 1,3-dicarbonyl compounds with Bismuth (III) sulfate trihydrate have been synthesized. MCR of benzaldehyde, ethyl acetoacetate, and urea as a model reaction was chosen for optimization. Results are shown in Table 2. With Bismuth (III) sulfate trihydrate as the catalyst, the reaction rate increases dramatically and is easily removed and reused (Table 2). As shown in Table 1, there is no decrease in catalytic efficiency (entry 12). All reactions were monitored by TLC and forwarded to maximize atom utilization. All compounds with melting points, IR, ¹H NMR, ¹³C NMR, and CHN techniques were identified. Different aldehydes donating/electron withdrawing for synthesis of DHPMs reacted with excellent yield in available time.

Table 2: Bismuth (III) sulfate trihydrate catalyzed synthesis of 3,4-dihydropyrimidinones/thiones derivatives.

Entry
Compound
Substitution
X
M.p. (°C)
Yield (%)

1
5a
H
O
203-204
89

2
5b
4-Methoxy
O
202-203
92

3
5c
4-Nitro
O
212–214
95

4
5d
4-Chloro
O
215-216
93

5
5e
3-Chloro
O
192-193
93

6
5f
4-Fluro
O
182–184
90

7
5g
H
S
208–210
88

8
5h
3-Nitro
S
206–208
86

9
5i
4-Methoxy
S
156–158
86

10
5j
2-Chloro
S
218–220
80

11
5k
2-Nitro
S
190–192
81

12
5m
3-Methoxy
S
160–162
85

Reaction conditions: 2 mmol aldehyde, 2.5 mmol ethyl acetoacetate, 2.5 mmol urea/thiourea, and Bismuth (III) sulfate trihydrate (10 mol%) were refluxed with stirring for 60 min.

The catalyst was easily recovered by simple filtration after dilution of the reaction mixture with ethyl acetate and was reused after being vacuum dried. Bi₂(SO₄)₃ was reused for four runs without significant loss of activity (Run 1: 91%; Run 2: 89%; Run 3: 87%; Run 4: 85%).

In order to standardize the reaction conditions for the condensation reaction, it was decided to synthesize 3,4-dihydropyrimidin-2(1H)-one (5a) from benzaldehyde, urea, and ethyl acetoacetate using Bismuth (III) sulfate trihydrate, and we found that the reaction is fast when compared to other reported methods. The results are compared with the reported methods, and it is clear from Table 3 that the present method is more efficient.

Table 3: Biginelli synthesis of 5-ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one: Bismuth (III) sulfate trihydrate in comparison with some recent reports.

Entry
Conditions
Time (h:min)
Yield (%)
Reference

1
Al(NO₃)₃·9H₂O/SF, 80°C
0:15
98
[13]

2
Sulfated tungstate/SF, 80°C
1:00
92
[13]

3
PPA-SiO₂/CH₃CN, reflux
1:00
88
[13]

4
FeCl₃ immobilized in Al-MCM 41/CH₃CN, reflux
4:00
85
[13]

5
[Hmim] HSO₄/solvent-free, 110°C
0:20
92
[13]

6
Alpha-zirconium sulfophenylphosphonate/SF, 80°C
18:0
89
[13]

7
1, 3-Dichloro-5, 5-dimethylhydantoin/CH₃CN, reflux
4:00
89
[13]

Bi(NO₃)₃
1:30
92
[23]

8
Bismuth (III) sulfate trihydrate/SF, 90°C
1:00
89
In this research

4. Conclusion

In conclusion, our Bismuth (III) sulfate trihydrate as a catalyst for the synthesis of dihydropyrimidinones/thiones replaced under solvent-free conditions is displayed. Moderate to good yields of the corresponding DHPMs were obtained. Good yields, One-pot, reused, available time and simple separation experiments under solvent-free conditions with reused catalyst are advantages of this method.

Conflict of Interests

The author declares no financial conflict of interests.

Acknowledgment

The author gratefully acknowledges the financial support from the Research Council of Tonekabon Branch, Islamic Azad University.

References

T. Yue, M.-X. Wang, D.-X. Wang, G. Masson, and J. Zhu, “Catalytic asymmetric Passerini-type reaction: chiral aluminum-organophosphate-catalyzed enantioselective α-addition of isocyanides to aldehydes,” Journal of Organic Chemistry, vol. 74, no. 21, pp. 8396–8399, 2009.

B. A. Trofimov, L. V. Andriyankova, K. V. Belyaeva et al., “C2-functionalization of 1-substituted imidazoles with aldehydes and electron-deficient acetylenes: a novel three-component reaction,” European Journal of Organic Chemistry, no. 9, pp. 1772–1777, 2010.

N. Ma, B. Jiang, G. Zhang, S.-J. Tu, W. Wever, and G. Li, “New multicomponent domino reactions (MDRs) in water: highly chemo-, regio- and stereoselective synthesis of spiro{[1,3]dioxanopyridine}-4,6-diones and pyrazolo[3,4-b]pyridines,” Green Chemistry, vol. 12, no. 8, pp. 1357–1361, 2010.

B. Willy and T. J. J. Müller, “Regioselective three-component synthesis of highly fluorescent 1,3,5-trisubstituted pyrazoles,” European Journal of Organic Chemistry, no. 24, pp. 4157–4168, 2008.

M. M. Heravi, B. Baghernejad, H. A. Oskooie, and R. Hekmatshoar, “A novel and facile synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones via a one-pot multi-component reaction,” Tetrahedron Letters, vol. 49, no. 42, pp. 6101–6103, 2008.

M. Adib, E. Sheikhi, A. Kavoosi, and H. R. Bijanzadeh, “Synthesis of 2-(alkylamino)-5-{alkyl[(2-oxo-2H-chromen-3-yl)carbonyl]amino}-3,4-furandicarboxylates using a multi-component reaction in water,” Tetrahedron, vol. 66, no. 47, pp. 9263–9269, 2010.

W.-B. Chen, Z.-J. Wu, Q.-L. Pei, L.-F. Cun, X.-M. Zhang, and W.-C. Yuan, “Highly enantioselective construction of spiro[4H-pyran-3,3′-oxindoles] through a domino knoevenagel/Michael/Cyclization sequence catalyzed by cupreine,” Organic Letters, vol. 12, no. 14, pp. 3132–3135, 2010.

S.-L. Wang, F.-Y. Wu, C. Cheng et al., “Multicomponent synthesis of poly-substituted benzo[a]pyrano-[2, 3-c]phenazine derivatives under microwave heating,” ACS Combinatorial Science, vol. 13, no. 2, pp. 135–139, 2011.

S. R. Kolla and Y. R. Lee, “Efficient one-pot synthesis of β-phosphono malonates and 2-amino-4H-chromen-4-ylphosphonate derivatives by ethylenediamine diacetate-catalyzed three-component reactions,” Tetrahedron, vol. 68, no. 1, pp. 226–237, 2012.

C. O. Kappe, “100 years of the Biginelli dihydropyrimidine synthesis,” Tetrahedron, vol. 49, no. 32, pp. 6937–6963, 1993.

C. O. Kappe, “Recent advances in the Biginelli dihydropyrimidine synthesis: new tricks from an old dog,” Accounts of Chemical Research, vol. 33, no. 12, pp. 879–888, 2000.

P. Biginelli, “Aldehyde-urea derivatives of aceto- and oxaloacetic acids,” Gazzetta Chimica Italiana, vol. 23, pp. 360–413, 1893.

E. Kolvari and M. Mirzaeeyan, “Al(NO₃)₃9H₂O: an efficient catalyst for the one-pot synthesis of 3, 4-dihydropyrimidin-2(1H)-ones both under reflux or solvent-free conditions,” Journal of Chemistry, vol. 2013, Article ID 325268, 5 pages, 2013.

C. V. Reddy, M. Mahesh, P. V. K. Raju, T. R. Babu, and V. V. N. Reddy, “Zirconium(IV) chloride catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Tetrahedron Letters, vol. 43, no. 14, pp. 2657–2659, 2002.

M. G. Kulkarni, S. W. Chavhan, M. P. Shinde et al., “Zeolite catalyzed solvent-free one-pot synthesis of dihydropyrimidin-2(1H)-ones: a practical synthesis of monastrol,” Beilstein Journal of Organic Chemistry, vol. 5, article 4, 2009.

P. Salehi, M. Dabiri, M. A. Zolfigol, and M. A. Bodaghi Fard, “Silica sulfuric acid: an efficient and reusable catalyst for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones,” Tetrahedron Letters, vol. 44, no. 14, pp. 2889–2891, 2003.

E. H. Hu, D. R. Sidler, and U.-H. Dolling, “Unprecedented catalytic three component one-pot condensation reaction: an efficient synthesis of 5-alkoxycarbonyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones,” Journal of Organic Chemistry, vol. 63, no. 10, pp. 3454–3457, 1998.

F. Xu, J.-J. Wang, and Y.-P. Tian, “New procedure for one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones by Biginelli reaction,” Synthetic Communications, vol. 38, no. 8, pp. 1299–1310, 2008.

I. Cepanec, M. Litvić, M. Filipan-Litvić, and I. Grüngold, “Antimony(III) chloride-catalysed Biginelli reaction: a versatile method for the synthesis of dihydropyrimidinones through a different reaction mechanism,” Tetrahedron, vol. 63, no. 48, pp. 11822–11827, 2007.

S. K. De and R. A. Gibbs, “Ruthenium(III) chloride-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones under solvent-free conditions,” Synthesis, no. 11, pp. 1748–1750, 2005.

A. M. Elmaghraby, I. A. Mousa, A. A. Harb, and M. Y. Mahgoub, “Three component reaction: an efficient synthesis and reactions of 3, 4-dihydropyrimidin-2(1H)-ones and thiones using new natural catalyst,” ISRN Organic Chemistry, vol. 2013, Article ID 706437, 13 pages, 2013.

E. Abbasi and F. Hatamjafari, “Glutamic acid as an efficient catalyst for synthesis of dihydropyrimidinones,” Oriental Journal of Chemistry, vol. 29, no. 2, pp. 731–733, 2013.

M. A. Chari, D. Shobha, T. K. Kumar, and P. K. Dubey, “Bismuth (III) nitrate catalyzed one-pot synthesis of 3,4-dihydro-pyrimidin-2-(1H)-ones: an improved protocol for the Biginelli reaction,” Arkivoc, vol. 2005, no. 15, pp. 74–80, 2005.

N. Komatsu, M. Uda, and H. Suzuki, “Bismuth(III) halides and sulfate as highly efficient catalyst for the sulfenylation of carbonyl and related compounds,” Synlett, vol. 9, pp. 984–988, 1995.

H. Slimi, Y. Moussaoui, and R. b. Salem, “Synthesis of 3, 4-dihydropyrimidin-2(1H)-ones/thiones via Biginelli reaction promoted by bismuth(III) nitrate or PPh 3 without solvent,” Arabian Journal of Chemistry.

K. Ramalinga, P. Vijayalakshmi, and T. N. B. Kaimal, “Bismuth(III)-catalyzed synthesis of dihydropyrimidinones: improved protocol conditions for the Biginelli reaction,” Synlett, no. 6, pp. 863–865, 2001.

M. Syamala, “Recent progress in three-component reactions: an update,” Organic Preparations and Procedures International, vol. 41, no. 1, pp. 1–68, 2009.

J. M. Bothwell, S. W. Krabbe, and R. S. Mohan, “Applications of bismuth(III) compounds in organic synthesis,” Chemical Society Reviews, vol. 40, no. 9, pp. 4649–4707, 2011.