Scholarly article on topic 'Triphenylphosphine: An efficient catalyst for the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione under thermal conditions'

Triphenylphosphine: An efficient catalyst for the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione under thermal conditions Academic research paper on "Chemical sciences"

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{"4 / 6-diphenyl-3 / 4-dihydropyrimidine-2(1H)-thione" / Triphenylphosphine / "1 / 3-Diaryl-2-propen-1-one" / Chalcones}

Abstract of research paper on Chemical sciences, author of scientific article — K. Aswin, S. Sheik Mansoor, K. Logaiya, S.P.N. Sudhan

Abstract An efficient and direct procedure for the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione derivatives by condensation of 1,3-diaryl-2-propen-1-ones (chalcones) and thiourea in ethanol at 65°C using triphenylphosphine (PPh3) as a catalyst is reported. The method gave good yields of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione derivatives in short reaction times in comparison with earlier methods. The catalyst is recycled without loss of activity. Using non-toxic and inexpensive materials, simple work-up, short reaction times and high yields of the products are the advantages of this method.

Academic research paper on topic "Triphenylphosphine: An efficient catalyst for the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione under thermal conditions"

Journal of King Saud University - Science (2013) xxx, xxx-xxx

King Saud University Journal of King Saud University -Science

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ORIGINAL ARTICLE

Triphenylphosphine: An efficient catalyst for the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione under thermal conditions

K. Aswin, S. Sheik Mansoor *, K. Logaiya, S.P.N. Sudhan

Research Department of Chemistry, Bioactive Organic Molecule Synthetic Unit, C. Abdul Hakeem College, Melvisharam 632 509, Tamil Nadu, India

Received 10 March 2013; accepted 6 May 2013

KEYWORDS

4,6-diphenyl-3,4-dihydropy-

rimidine-2(1H)-thione;

Triphenylphosphine;

1,3-Diaryl-2-propen-1-one;

Chalcones

Abstract An efficient and direct procedure for the synthesis of 4,6-diphenyl-3,4-dihydropyrimi-dine-2(1H)-thione derivatives by condensation of 1,3-diaryl-2-propen-1-ones (chalcones) and thiourea in ethanol at 65 °C using triphenylphosphine (PPh3) as a catalyst is reported. The method gave good yields of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione derivatives in short reaction times in comparison with earlier methods. The catalyst is recycled without loss of activity. Using non-toxic and inexpensive materials, simple work-up, short reaction times and high yields of the products are the advantages of this method.

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1. Introduction

3,4-Dihydropyrimidin-2(1H)-ones (DHPM) and their sulfur analogs have been reported to possess remarkable pharmacological properties including antiviral, antitumor, antibacterial, anti-inflammatory and antioxidant activities (Kappe, 1993, 2000a,b; Russowsky et al., 2006; Stefani et al., 2006; Chitra et al., 2011). Dihydropyrimidinones have also exhibited important therapeutic and pharmacological properties as the integral backbones of several calcium channel blockers, calcium channel modulators, antihypertensive agents and a-la-adrenergic

receptor antagonists (Atwal et al., 1990; Rovnyak et al., 1995; Nagarathnam et al., 1999). Several alkaloids isolated from marine sources also exhibit interesting biological activities, molecular structures of which contain the dihydropyri-midinone moiety. In particular, the batzelladine alkaloids have been found to be potent HIV gp-120-CD4 inhibitors (Pa-til et al., 1995; Snider et al., 1996). Therefore, in consequence of their valuable biological activities, great interest has been established in the preparation of pyrimidin-2(1 H)-ones.

The first protocol to prepare compounds of this type was presented by Biginelli in 1893 and involved a three-component, one-pot condensation of benzaldehyde, ethyl acetoacetate and urea under strongly acidic conditions (Biginelli, 1893). However, this reaction often requires harsh conditions and long reaction times and affords low yields, particularly when substituted aromatic and aliphatic aldehydes are employed. The scope of the original Biginelli reaction was gradually extended by the variation of all three building blocks, allowing access to

* Corresponding author. Tel.: +91 9944093020. E-mail address: smansoors2000@yahoo.co.in (S.S. Mansoor). Peer review under responsibility of King Saud University.

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a large number of multi-functionalized dihydropyrimidineone derivatives.

The most direct procedure for the preparation of dihydro-pyrimidinones and thiones is through condensation of b-dicar-bonyl compounds with an aromatic aldehyde and urea or thiourea in the presence of Lewis and Bransted acid promoters such as silica immobilized nickel complex (Sharma and Rawat, 2012), cellulose sulfuric acid (Rajack et al., 2013), bioglycerol-based sulfonic acid functionalized carbon (Konkala et al., 2012), perchloric acid doped silica (Narahari et al., 2012), mel-amine trisulfonic acid (Shirini et al., 2011), sulfonated carbon (Moghaddas et al., 2012) and so on. The derivatives of 3,4-dihydro-4,6-diarylpyrimidin-2(1H)-one are a class of pyrimi-din-2(1 H)-one skeletons which were prepared via two more common procedures: through the reaction of a, b-unsaturated ketones and urea/thiourea (Safaei-Ghomi and Ghasemzdeh, 2011) or through condensation reaction of acetophenone derivatives, aldehydes and urea/thiourea using various Bransted and Lewis acid catalysts (Pourghobadi and Derikv-and, 2010; Khosropour et al., 2006; Heravi et al., 2008; Shar-ghi and Jokar, 2009; Lei et al., 2009; Wang et al., 2010; Oskooie et al., 2011; Liu et al., 2013; Chitra et al., 2011). Some of these newer reported methods, however, exhibit drawbacks such as unsatisfactory yields, cumbersome product isolation procedures, and environmental pollution. Moreover, the main disadvantage of almost all existing methods is that the catalysts are destroyed in the work-up procedure and cannot be recovered or reused. There is still a need, therefore, for versatile, efficient, simple and environmentally friendly processes for the formation of DHPM derivatives.

Since Lewis acids have already been used as catalysts for the synthesis of 4,6-diarylpyrimidine-2(1 H)-one derivatives, it was thought to develop the synthesis of 4,6-Diphenyl-3,4-dihydro-pyrimidine-2(1 H)-thione derivatives using a Lewis base catalyst. In this respect, it is previously reported that the Biginelli condensation can be easily achieved with a catalytic amount of triphen-ylphosphine as a Lewis base (Mansoor et al., 2011) and this method is very flexible and also enables the preparation of a large number of 3,4-dihydropyrimidin-2-ones/thiones/imines.

Considering the potential of developing new routes to the synthesis of heterocyclic compounds (Mansoor et al., 2013; Mansoor et al., 2012a,b; Ghashang et al., 2013), the present investigation aimed toward the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione derivatives using condensation reaction of 1,3-diaryl-2-propen-1-one derivatives and thio-urea in the presence of triphenylphosphine as catalyst.

2. Materials and methods

2.1. Apparatus and analysis

Commercially available laboratory grade chemicals with high purity were used. Triphenylphosphine is used as catalyst. The benzaldehydes used were with substituents H, p-Cl, p-Br, p-CH3, p-OCH3, p-F, m-CH3, and m-OCH3. The solid aldehydes were used as such and the liquid aldehydes were used after vacuum distillation. Acetopheones with substituents H, m-CH3, m-OCH3, p-Br, and p-CH3, and thiourea were used in the synthesis of various 4,6-diphenyl-3,4-dihydropyrimi-dine-2(1 H)-thiones. The solvents like methanol, ethanol, ace-tonitrile, 1,4-dioxane and cyclohexane were used to study the

optimization of solvent. Analytical thin-layer chromatography was performed with E. Merck silica gel 60F glass plates. 'H-NMR (500 MHz) and 13C-NMR (125 MHz) spectra were obtained using Bruker DRX- 500 Avance at ambient temperature, using TMS as internal standard. Fourier-transform infrared spectra were obtained as KBr disks on Shimadzu spectrometer. Mass spectra were determined by employing Varion - Saturn 2000 GC/MS instrument while elemental analyses were measured by Perkin Elmer 2400 CHN elemental analyzer flowchart. All yields refer to isolated products unless otherwise stated.

2.2. General procedure for the preparation of pyrimidine-2-thione derivatives (3a-l)

A mixture of 1,3-diaryl-2-propen-1-one (2 mmol), thiourea (3 mmol) and PPh3 (0.2 mmol) was refluxed with stirring at 65 0C in ethanol as solvent and the progress of the reaction monitored by TLC. Subsequently, the reaction mixture was left overnight, concentrated under reduced pressure, the residue collected, washed with water and recrystallized from ethanol to afford the pure product. The catalyst is removed by filtration and the recovered catalyst can be washed consequently with an aliquot of fresh CH2Cl2 (2 x 10 mL), water and then acetone. After drying, it can be reused without noticeable loss of reactivity. All the products obtained were fully characterized by spec-troscopic methods such as IR, 'H-NMR, 13C-NMR, mass spectroscopy and elemental analysis and have been identified by the comparison of the spectral data with those reported.

3. Results

We have prepared a series of 4,6-diphenyl-3,4-dihydropyrimi-dine-2(1H)-thione derivatives from a mixture of 1,3-diaryl-2-propen-1-one derivatives (2 mmol) and thiourea (3 mmol) and our results are presented here.

Among various catalyst tested, PPh3 was found to be an effective catalyst wherein the product was obtained in good yields under mild conditions (Table 1). With PPh3 as catalyst, next the effect of various solvents such as methanol, ethanol, acetonitrile, 1,4-dioxane and cyclohexane and also solvent-free condition was screened (Table 2; entries 1-5). The reaction was completed within 5 h and the expected product was obtained in 94% yield in ethanol. Under the optimized set of reaction conditions a number of 1,3-diaryl-2-propen-1-one derivatives (1) were allowed to react with thiourea (2) in the presence of PPh3 (0.2 mmol) in ethanol at 65 0C (Scheme 1). The results are given in Table 3.

3.1. The spectroscopic and analytical data for the synthesized compounds are presented below (3a—l)

3.1.1. 4,6-Diphenyl-3,4-dihydropyrimidine-2(1H)-thione (3a) IR (KBr, cm—1): 3173 (NH), 1644 (C=N), 1544, 1470 (C=C), 1183 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 4.90 (1H, d, J = 5.0 Hz, 4-CH), 5.22 (1H, d, J = 5.0 Hz, 5-CH), 6.92-7.44 (10H, m, Ar-H), 8.80 (1H, bs, NH), 9.66 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 54.9, 102.1, 126.0, 126.8, 127.4,128.5,129.4,129.8,133.6,134.5,144.4,176.0 ppm; MS(E-SI): m/z 267 (M + H) + ; Anal. Calcd for C16H14N2S: C, 72.18; H, 5.26; N, 10.52%. Found: C, 72.13; H, 5.22; N, 10.52%.

Table 1 Synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione: catalyst screeninga.

Entry Catalyst Amount of catalyst (mmol) Time (h) Yield (%)b

1 None - 8 20

2 AlCl3 1 6 38

3 ZnCl2 1 6 40

4 FeCl3 1 6 52

6 BiCl3 0.2 6 72

7 BiBr3 0.2 6 76

11 PPh3 0.4 5 86

12 PPh3 0.2 5 94

13 PPh3 0.1 5 86

14 PPh3 0.06 5 80

a Reaction conditions: b Isolated yields. 1,3-diphenyl-2-propen-1- one (2 mmol), and thiourea (3 mmol) heating at 65 °C in ethanol.

Table 2 Synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione: solvent screeninga.

Entry Solvent Amount of catalyst (mmol) Time (h) Yield (%)b

1 Methanol 0.2 5 85

2 Ethanol 0.2 5 94

3 Acetonitrile 0.2 5 65

4 1,4-Dioxane 0.2 5 60

5 Cyclohexane 0.2 5 52

6 None 0.2 5 74

a Reaction conditions: 1,3-diphenyl-2-propen-1- one (2 mmol) and thiourea (3 mmol) heating at 65 °C in the presence of PPh3 (0.2 mmol) with

various solvents (5 ml).

b Isolated yields.

H2N NH 2 2

4-Cl 4-Br 4-F

4-CH3 Ri 4-OCH3 3-CH3 3-OCH3

R2 = 4-Br

4-CH3 3-CH3 3-OCH3

S 3a-l

Scheme 1 Synthesis of various 4,6-diphenyl-3,4-dihydropyrimi-dine-2(1H)-thione derivatives.

3.1.2. 4-(4-Chlorophenyl)-6-phenyl-3,4-dihydropyrimidine-2(lH)-thione (3b)

IR (KBr, cm-1): 3152 (NH), 1655 (C=N), 1548, 1472 (C=C), 1180 (C=S). 'H-NMR (500 MHz, DMSO-d6) d: 4.88 (1H, d, J = 5.0 Hz, 4-CH), 5.28 (1H, d, J = 5.0 Hz, 5-CH), 7.037.55 (9H, m, Ar-H), 8.75 (1H, bs, NH), 9.71 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 50.6, 56.2, 100.4,

111.3, 121.3, 126.2, 126.7, 128.5, 129.1, 129.5, 132.1, 133.6,134.9, 155.5, 177.2 ppm; MS(ESI): m/z 301.45 (M + H) + ; Anal. Calcd for C16H13ClN2S: C, 63.90; H, 4.33; N, 9.32%. Found: C, 63.88 H, 4.31; N, 9.31%.

3.1.3. 4-(4-Bromophenyl)-6-phenyl-3,4-dihydropyrimidine-2(1H)-thione (3c)

IR (KBr, cm-1): 3145 (NH), 1646 (C=N), 1540, 1472 (C=C), 1182 (C=S). 1H-NMR (500 MHz, DMSO-d6) d:4.87 (1H, d, J = 5.0 Hz, 4-CH), 5.19 (1H, d, J = 5.0 Hz, 5-CH), 7.08-7.3 (9H, m, Ar-H), 8.88 (1H, bs, NH), 9.77 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 50.2, 55.9, 100.3, 111.5, 121.1, 126.3, 126.9, 128.4, 129.1, 129.2, 132.5, 133.7,134.4, 155.5, 178.0 ppm; MS(ESI): m/z 345.9 (M + H) + ; Anal. Calcd for C16H13BrN2S: C, 55.66; H, 3.77; N, 8.12%. Found: C, 55.64; H, 3.74; N, 8.10%.

3.1.4. 4-(4-Methylphenyl)-6-phenyl-3,4-dihydropyrimidine-2(1H)-thione (3d)

IR (KBr, cm-1): 3188(NH), 1652 (C=N), 1560, 1484 (C=C), 1184 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 2.03 (3H, s, CH3), 4.82 (1H, d, J = 5.0 Hz, 4-CH) 5.16 (1H, d, J= 5.0 Hz, 5-CH), 6.96-7.42 (9H, m, Ar-H), 8.83 (1H, bs, NH), 9.64 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 21.2, 56.0, 102.5, 127.3, 127.7,128.6, 129.5, 130.5,

130.4, 134.9, 138.6, 142.4, 178.5 ppm; MS(ESI): m/z 281 (M + H) + ; Anal. Calcd for C17H16N2S: C, 72.85; H, 5.71; N, 10.00%. Found: C, 72.81; H, 5.70; N, 10.01%.

3.1.5. 4-(4-Methoxyphenyl)-6-phenyl-3,4-dihydropyrimidine-2(1H)-thione (3e)

IR (KBr, cm-1): 3156 (NH), 1658 (C=N), 1564, 1488 (C=C), 1186 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 3.60 (3H, s, -OCH3), 4.89 (1H, d, J = 5.0 Hz, 4-Ch) 5.19 (1H, d, J = 5.0 Hz, 5-CH), 6.88-7.44 (9H, m, Ar-H),8.74 (1H, bs, NH), 9.72 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-

Table 3 Synthesis of various 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thionea

Entry Chalcones

Product Time (h) Yield (%)b Mp (oC)

Found Reported"

180-182 182-184

156-158

144-146

197-199 198-200

124-126 123-124

186-188

182-184 183-185

140-142

(continued on next page)

Table 3 (continued)

Entry Chalcones

Product Time (h)

Yield (%)b

Mp (oC)

Reportedc

178-180

166-168

196-198

180-182

a Reaction conditions: 1,3-diphenyl-2-propen-1-one (2mmol) and thiourea (3 mmol) heating at 65 °C in the presence of PPh3 (0.2mmol) in ethanol. b Isolated yield.

c Safaei-Ghomi and Ghasemzdeh (2011).

d6) d: 50.2, 56.0, 100.4, 111.4, 121.1, 126.4, 128.6, 129.1, 129.6, 132.1, 135.1, 156.0,178.0 ppm; MS(ESI): m/z 297 (M + H) + ; Anal. Calcd. for C17H16N2OS: C 68.92, H 5.41, N 9.46%. Found: C 68.68, H 5.38, N 9.40%.

3.1.6. 4-(4-Fluorophenyl)-6-phenyl-3,4-dihydropyrimidine-2(1H)-thione (3f)

IR (KBr, cm-1): 3144 (NH), 1650 (C=N), 1558, 1482 (C=C), 1190 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 4.92 (1H, d, J = 5.0 Hz, 4-CH) 5.22 (1H, d, J = 5.0 Hz, 5-CH), 6.93-7.33 (9H, m, Ar-H), 8.85(1H, bs, NH), 9.81 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 51.4, 55.8, 100.3, 111.5, 121.1, 125.8, 126.7, 128.7, 129.3, 129.8, 132.3, 133.6,134.7, 155.3, 177.7 ppm; MS(ESI): m/z 285 (M + H) + ; Anal. Calcd for C16H13FN2S: C, 67.60; H, 4.57; N, 9.86%. Found: C, 67.50; H, 4.54; N, 9.84%.

3.1.7. 4-(3-Methylphenyl)-6-phenyl-3,4-dihydropyrimidine-2(1H)-thione (3g)

IR (KBr, cm-1): 3177 (NH), 1638 (C=N), 1566, 1477 (C=C), 1194 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 2.08 (3H, s, CH3), 4.83 (1H, d, J = 5.0 Hz, 4-CH) 5.24 (1H, d, J = 5.0 Hz, 5-CH), 6.83-7.31 (9H, m, Ar-H), 8.80 (1H, bs, NH), 9.74 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-

d6) d: 55.5, 101.5, 124.2, 126.4, 127.6,127., 128.7, 129.2, 129.6, 133.5, 134.6, 138.2, 144.8, 178.0 ppm; MS(ESI): m/z 281 (M + H) + ; Anal. Calcd for C17H16N2S: C, 72.85; H, 5.71; N, 10.00%. Found: C, 72.83; H, 5.69; N, 10.02%.

3.1.8. 4-(3-Methoxyphenyl)-6-phenyl-3,4-dihydropyrimidine-2(1H)-thione (3h)

IR (KBr, cm-1): 3152 (NH), 1656 (C=N), 1555, 1479 (C=C), 1188 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 3.60 (3H, s, -OCH3), 4.87 (1H, d, J = 5.0 Hz, 4-CH), 5.14 (1H, d, J = 5.0 Hz, 5-CH), 6.90-7.20 (9H, m, Ar-H), 8.79(1H, bs, NH), 9.82 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 50.8, 56.5, 100.3, 111.8, 121.3, 126.6, 126.9, 128.5, 129.1, 129.5, 131.9, 133.5,134.5, 155.4, 176.9 ppm; MS(ESI): m/z 297 (M + H) + ; Anal. Calcd. for C17H16N2OS: C 68.92, H 5.41, N 9.46%. Found: C 68.88, H 5.40, N 9.44%.

3.1.9. 4-Phenyl-6-(3-methylphenyl)-3,4-dihydropyrimidine-2(1H)-thione (3i)

IR (KBr, cm-1): 3152 (NH), 1662 (C=N), 1540, 1482 (C=C), 1192 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 2.11 (3H, s, -CH3), 4.89 (1H, d, J = 5.0 Hz, 4-CH), 5.20 (1H, d, J = 5.0 Hz, 5-CH), 6.99-7.46 (9H, m, Ar-H), 8.81(1H, bs, NH), 9.66 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 50.5, 56.3,

100.1, 111.3, 121.1, 126.2, 126.6, 128.4, 129.1, 129.6, 132.1,

133.6.134.6, 155.5, 177.5 ppm; MS(ESI): m/z 281 (M + H) + ; Anal. Calcd for C17H16N2S: C, 72.85; H, 5.71; N, 10.00%. Found: C, 72.80; H, 5.67; N, 10.04%.

3.1.10. 4-Phenyl-6-(3-methoxyphenyl)-3,4-dihydropyrimidine-2(1H)-thione (3j)

IR (KBr, cm-1): 3148 (NH), 1661 (C=N), 1550, 1470 (C=C), 1191 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 3.60 (3H, s, -OCH3), 4.90 (1H, d, J = 5.0 Hz, 4-CH), 5.21 (1H, d, J = 5.0 Hz, 5-CH),7.06-7.38 (9H, m, Ar-H), 8.73(1H, bs, NH), 9.79 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 50.6, 55.9, 101.3, 110.8, 120.8, 126.7, 127.1, 128.8, 129.1, 129.4, 132.4, 133.4,134.6, 155.1, 177.9 ppm; MS(ESI): m/z 297 (M + H) + ; Anal. Calcd. for C17H16N2OS: C 68.92, H 5.41, N 9.46%. Found: C 68.90, H 5.38, N 9.43%.

3.1.11. 4-(4-Fluorophenyl)-6-(4-bromophenyl)-3,4-dihydropyrimidine-2(1H)-thione (3k)

IR (KBr, cm-1): 3161 (NH), 1654 (C=N), 1554, 1473 (C=C), 1187 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 4.94 (1H, d, J = 5.0 Hz, 4-CH), 5.19 (1H, d, J = 5.0 Hz, 5-CH), 6.927.32 (8H, m, Ar-H), 8.91 (1H, bs, NH), 9.76 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 50.6, 56.4, 101.5, 111.0, 121.0, 126.5, 126.9, 128.4, 129.4, 129.8, 132.1,

133.8.134.7, 155.0, 177.9 ppm; MS(ESI): m/z 363.9 (M + H) + ; Anal. Calcd for C16H12BrFN2S: C, 52.90; H, 3.30; N, 7.71%. Found: C, 52.88; H, 3.28; N, 7.68%.

3.1.12. 4-(4-Chlorophenyl)-6-(4-methylphenyl)-3,4-dihydropyrimidine-2(1H)-thione (3l)

IR (KBr, cm-1): 3146 (NH), 1658 (C=N), 1549, 1475 (C=C), 1184 (C=S). 1H-NMR (500 MHz, DMSO-d6) d: 2.16 (3H, s, CH3) 4.92 (1H, d, J = 5.0 Hz, 4-CH), 5.18 (1H, d, J= 5.0 Hz, 5-CH), 6.97-7.37 (8H, m, Ar-H), 8.78 (1H, bs, NH), 9.82 (1H, bs, NH) ppm; 13C-NMR (125 MHz, DMSO-d6) d: 49.8, 55.8, 100.0, 111.3, 121.3, 126.5, 127.3, 128.9, 129.3, 129.7, 132.4, 133.9,134.7, 155.2, 174.3 ppm; MS(ESI): m/z 315.45 (M+ H) + ; Anal. Calcd for C17H15ClN2S: C, 64.87; H, 4.77; N, 8.90%. Found: C, 64.82; H, 4.73; N, 8.88%.

The structures of isolated products 3a-l were deducted by physical and spectroscopic data such as: IR, 1H-NMR and 13C-NMR spectroscopy, mass and elemental analysis. In IR spectra, the stretching frequency of NH is formed in the region between m = 3144-3188 cm-1. The stretching vibration of C-N appeared in the region between m = 1638-1655 cm-1. The stretching frequency of C=S is formed in the region between m = 1180-1194 cm-1. In the 1H-NMR spectra of compound 3a, the two signals around d = 8.80 and d = 9.66 ppm correspond to two NH groups at N-1 and N-3 in the product. Presence of these two signals confirmed the formation of desired products in the reaction.

4. Discussion

A novel and efficient procedure for the synthesis of 4,6-diphe-nyl-3,4-dihydropyrimidine-2(1H)-thione derivatives by the reaction of 1,3-diaryl-2-propen-1-one derivatives and thiourea in the presence of PPh3 as a catalyst is described. Triphenyl phosphine has been widely used, however as an effective catalyst for the synthesis via multicomponent reaction of

Table 4 Synthesis 2(1H)-thionea.

of 4,6-diphenyl-3,4-dihydropyrimidine-

Entry Cycle Time (h) Yield (%)b

1 0 5.0 94

2 1 5.0 92

3 2 5.0 90

4 3 5.0 87

a Reaction conditions: 1,3-diphenyl-2-propen-1-one (2 mmol) and thiourea (3 mmol) heating at 65 °C in the presence of PPh3 (0.2 mmol) in ethanol. b Isolated yield.

1,4-dihydropyridine derivatives (Debache et al., 2009), 3,4-dihydropyrimidine derivatives (Debache et al., 2008), y-buty-rolactone derivatives and highly substituted enones (Bayat et al., 2010) and silyl esters (Liu et al., 2007).

Initially, the cyclo-condensation reaction of 1,3-diaryl-2-propen-1-one (1) and thiourea (2) as a model substrate was investigated to optimize the reaction conditions. At the beginning, the model reaction was carried out to represent a selection of Lewis acids, including AlCl3, ZnCl2, FeCl3, BiCl3, BiBr3, and PPh3 in ethanol at 65 °C (Table 1). It was noted that the best yields are obtained when 0.2 mmol of PPh3 was used (Table 1).

It was noted that solvents played an important role in the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione derivatives. It was found that the best results were obtained in ethanol with 0.2 mmol of PPh3 as catalyst at 65 °C (Table 2; entry 2).

Generally aldehydes bearing both electron-donating and electron-withdrawing groups resulted in the corresponding product in good to excellent yields. The advantage of the present protocol is the use of PPh3 which can be easily recovered and reused several times without any loss in its activity (Table 4) (Fig. 1). The reaction is also characterized by its operational simplicity and high yield of products.

100989694929088 86 84 82 80

Recyclability of catalyst PPh3

12 3 4

Number of Runs

Figure 1 Recyclability of PPh3 for the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione. Yield (%) of the product and number of runs of catalyst PPh3 are shown.

5. Conclusion

In conclusion, an efficient process has been developed for the synthesis of 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione derivatives from the reaction of 1,3-diaryl-2-propen-1-one derivatives and thiourea in the presence of PPh3 (0.2 mmol) at 65 0C in ethanol. All the synthesized compounds were fully characterized by spectroscopic methods such as IR, 'H-NMR, 13C-NMR, mass spectroscopy and elemental analysis. The simplicity of this procedure, together with the eco-friendly nature represents the main advantages of this method. We expect this method will find extensive applications in the field of drug discovery.

The catalyst can be easily recovered, regenerated and reused without loss of its activity, thus providing an economic and environmentally friendly method for other organic reactions.

Acknowledgement

The authors gratefully acknowledge University Grants Commission, Government of India, New Delhi for financial support (Major Research Project: F. No. 40-44 / 2011(SR)).

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