International Scholarly Research Notices

International Scholarly Research Notices / 2012 / Article

Research Article | Open Access

Volume 2012 |Article ID 480989 | https://doi.org/10.5402/2012/480989

Srinivasa Rao Jetti, Divya Verma, Shubha Jain, "An Efficient One-Pot Green Protocol for the Synthesis of 5-Unsubstituted 3,4-Dihydropyrimidin-2(1H)-Ones Using Recyclable Amberlyst 15 DRY as a Heterogeneous Catalyst via Three-Component Biginelli-Like Reaction", International Scholarly Research Notices, vol. 2012, Article ID 480989, 8 pages, 2012. https://doi.org/10.5402/2012/480989

An Efficient One-Pot Green Protocol for the Synthesis of 5-Unsubstituted 3,4-Dihydropyrimidin-2(1H)-Ones Using Recyclable Amberlyst 15 DRY as a Heterogeneous Catalyst via Three-Component Biginelli-Like Reaction

Academic Editor: J. M. Campagne
Received02 Sep 2012
Accepted24 Sep 2012
Published22 Nov 2012

Abstract

An environmentally benign green protocol for the synthesis of 5-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones using Amberlyst 15 DRY as a recyclable catalyst has been developed. The use of resinous, nontoxic, thermally stable, and inexpensive Amberlyst 15 DRY, as a recyclable heterogeneous catalyst, makes the process simple with negligible chemical waste. Among the various solid acid catalysts Amberlyst 15 DRY was found to be the most efficient catalyst with regard to reaction time, yield, and ease of work-up procedure.

1. Introduction

Replacement of conventional, toxic, and polluting Bronsted and Lewis acid catalysts with ecofriendly reusable solid acid heterogeneous catalysts like acidic zeolites, clays, sulfated zirconia, and ion exchange resins is an area of current interest [1, 2]. The use of solid acid catalyst instead of liquids includes many advantages, such as reduced equipment corrosion, ease of product separation, recycling of the catalyst, and environmental acceptability. In the recent past ion exchange resins in general and styrene-DVB matrix resin sulfonic acid (Amberlyst 15 DRY) in particular, which are strongly acidic and chemically as well as thermally stable, have been found to be excellent catalysts for a variety of the major organic reactions like esterification, alkylation, acylation, and condensation [38].

Pyrimidinones or dihydropyrimidinones (DHPMs) are well known for their wide range of bioactivities. Their applications in the field of drug research have stimulated the development of a wide range of synthetic methods for their preparation and chemical transformations. Out of the five major bases in nucleic acids three are pyrimidine derivatives which comprise of cytosine (1) which is found in DNA and RNA, uracil (2) in RNA and thymine, and (3) in DNA. Because of their involvement as bases in DNA and RNA, they have become very important in the world of synthetic organic chemistry. Aryl-substituted 3,4-dihydropyrimidin-2(1H)-one and their derivatives are an important class of substances in organic and medicinal chemistry (see Figure 1).

4-Aryl-1,4-dihydropyridines (DHPMs) of the Nifedipine type (4) [9] were first introduced into clinical medicine in 1975 and are still the most potent group of calcium channel modulators available for the treatment of cardiovascular diseases [10]. Dihydropyrimidines of type (5) show a very similar pharmacological profile, and in recent years, several related compounds were developed (5) that are equal in potency and duration of antihypertensive activity to classical and second-generation dihydropyridinedrugs [11]. (see Figure 2).

In an attempt to prepare DHPMs, different types of acidic catalysts such as H2SO4 [12], BF3·EtOH/CuCl [13], LaCl3·7H2O with catalytic concentrated HCl [14], CeCl3·7H2O [15], InCl3 [16], heteropolyacids [17], BiCl3 [18], Cu(OTf)2 [19], TMSCl [20], LiClO4 [21], LiBr [22], InBr3 [23], phenyl pyruvic acid [24], FeCl3·6H2O/HCl [25], TMSI [26], CdCl2 [27], CuCl2·2H2O–HCl [28], and ZnBr2 [29] have been used. However, inspite of their potential utility many of the existing methods suffer from the drawbacks, such as the use of strong acidic conditions, longer reaction times, tedious workup, environmental disposal problems, and lower yields of the products, leaving scope for further development of an efficient and versatile method for Biginelli reaction.

Growing concern about environmental damage leads to an urgent requirement for the development of ecofriendly technology and economic processes. It is of great practical importance to synthesize DHPM derivatives by the Biginelli reaction by using a solid acid catalyst, because of the ability to modify the acid strength, ease of handling, recycling of the catalyst, and environmental compatibility. In view of the above requirement, and as a part of our program towards green synthesis, we herein report a single-step and ecofriendly protocol for the synthesis of DHPM derivatives by the multicomponent reactions of 1,3-dicarbonyl compound, aldehydes, and urea (Scheme 1) over Amberlyst 15 DRY with good yields and selectivity.

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2. Results and Discussion

To evaluate the catalytic effect of various ion exchange resins we started with the model reaction of ethylacetoacetate (1.0 mmol) with benzaldehyde (1.0 mmol) and urea (1.2 mmol) in refluxing ethanol without and with use of Amberlyst-70 and Amberlyst 15 DRY as catalysts to afford dihydropyrimidine 1a and the results obtained were compared with those already reported using other catalysts [30, 31] (Table 1). It can be seen from Table 1 that Amberlyst 15 DRY is the most efficient among the five solid acidic ion exchange resins. It was found that 50 mg of Amberlyst 15 DRY is sufficient to carry out the Biginelli reaction successfully. An increase in the amount of Amberlyst 15 DRY to more than 50 mg showed no substantial improvement in the yield, whereas the yield is reduced by decreasing the amount of Amberlyst 15 DRY.


EntryIon exchange resinReaction time (h)Yield (%)

110Trace
2Amberlyst-70381
3Amberlyst 15 DRYa5.594
4Indion-130392.5
5Indion-1903.592
6Nafion-H4.585
7Envirocat EPZ10684
8Montmorillonite KSF1038

aReaction conditions: ethyl acetoacetate (1.0 mmol), benzaldehyde (1.0 mmol), and urea (1.2 mmol) in dry ethanol (10 mL), ion exchange resin (50 mg) at refluxing temperature.

The effect of solvent on the reaction was studied (Table 2, entries 1–6) and ethanol was found to be the best solvent when considering the reaction yields and environmental damage.


EntryCatalystSolventTime (h)Yield (%)

1Amberlyst 15 DRYWater490
2Amberlyst 15 DRYEtOH5.594
3Amberlyst 15 DRYCH3CN6.585
4Amberlyst 15 DRYTHF687
5Amberlyst 15 DRYBenzene10Trace
6Amberlyst 15 DRYToluene10Trace

aAll reactions were conducted at reflux temperature of the solvent used.

The method can be used for wide range of reactants with different functional group. We have synthesized some novel compounds containing quinoline, pyrimidine, indole, and coumarin units (Table 3). All reactions proceeded expeditiously and delivered good yields with broad range of structurally diverse aromatic and heterocyclic aldehydes used in this condensation. , -Unsaturated aldehydes react selectively with aldehyde functional group, whereas acid sensitive heterocyclic aldehydes exclusively gave dihydropyrimidinones in high yield. We found that electron donating or withdrawing group on aromatic aldehydes gave almost good to excellent yield. In all the cases the pure product was isolated by simple filtration without use of any chromatography or cumbersome reaction workup.


EntryR1R2XProductsaYieldb (%)M.P (°C)

1C6H5EtO1a89205–207
24-(CH3O)–C6H4EtO1b90202-203
34-(NMe2)–C6H4EtO1c83254–256
44-NO2–C6H4EtO1d94212-213
54-(Cl)–C6H4EtO1e91214–215
64-(NO2)C6H4MeO1f95237–239
74-(CH3O)–C6H4MeO1g84192-193
8C6H5–CH=CHEtO1h94231–233
93-NO2–C6H4EtS1i92206-207
104-(CH3O)–C6H4EtS1j90154–156
11C4H4NEtO1k83180–182
12C4H3OEtO1l85211–213
13C4H3SEtO1m86201–203
14C8H6NEtO1n80212–214
15C5H4NEtO1o91193-194
16C5H4NEtS1p85168-169
17C9H6NEtO1q91245–247
18C4H3N2EtO1r89255–257
19C10H7EtO1s92182–185
20C9H5O3EtO1t89277–279

aReaction conditions: -ketoester (1.0 mmol), aldehyde (1.0 mmol), and urea/thiourea (1.2 mmol) in dry ethanol (10 mL), ion exchange resin (50 mg) at refluxing temperature. bIsolated yields.

The resin catalyst was separated from the reaction mixture by filtration and can be reused several times without any appreciable loss in activity, which clearly proves the recyclability and reusability of the catalyst (Figure 3). It is noteworthy to mention that these reactions are working well without using any phase transfer catalyst. Furthermore, the protocol has its advantages lying in the ease of separation of catalyst and the product, which can be achieved by simple filtration.

The formation of product 2 (Scheme 2) probably involves the activation of the carbonyl function by Amberlyst 15 DRY, thereby making the methyl group readily enolisable, which in turn reacts with aldehyde and urea-derived imine in a Michael-type step to produce 2 (Table 4).


EntryRProductsaYieldb (%)M.P (°C)

1C6H52a90233–236
24-(Cl)–C6H42b92267–269
34-(CH3)–C6H42c86248–250
44-(CH3O)–C6H42d84259–261
52-(Cl)–C6H42e91260–263
63-(CH3O) –C6H42f88256–258

aReaction conditions: acetophenone (1.0 mmol), benzaldehyde (1.0 mmol), and urea (1.5 mmol) in dry ethanol (10 mL), ion exchange resin (50 mg) at refluxing temperature. bIsolated yields.
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This investigation has been extended to cyclic ketones like cyclohexanone (Scheme 3). The products formed (3a–d) are listed in Table 5.


EntryRProductsaYieldb (%)M.P (°C)

1C6H53a93327–329
24-(NO2)C6H43b85341–343
34-(CH3)C6H43c89348–351
42-(Cl)–C6H43d88321–323

aReaction conditions: cyclohexanone (1.0 mmol), aldehyde (2.0 mmol), and urea (3.0 mmol) in dry ethanol (10 mL), ion exchange resin (50 mg) at refluxing temperature. bIsolated yields.
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3. Experimental

3.1. General

All solvents and reagents were purchased from Aldrich and Merck with high-grade quality and used without any purification. The Indion-130 and Indion-190 were purchased from Ion Exchange India Ltd. Nafion-H, Amberlyst-70, and Amberlyst 15 DRY were purchased from Aldrich. Melting points were determined on electrothermal apparatus by using open capillaries and are uncorrected. Thin-layer chromatography was accomplished on 0.2-mm precoated plates of silica gel G60 F254 (Merck). Visualization was made with UV light (254 and 365 nm) or with an iodine vapor. IR spectra were recorded on a FTIR-8400 spectrophotometer using DRS prob. 1H-NMR and 13C-NMR spectra were recorded in DMSO- solutions on a Bruker AVANCE 400NMR spectrometer operating at 400 (1H) and 100 (13C) MHz. LCMS analysis (EI, 70 V) was performed on a Hewlett-Packard HP 5971 instrument. All compounds were characterized by comparison of physical and spectral data with reported data [3235] (see Figure 4, Table 6).


Physical formOpaque beads
Ionic form as shipped Hydrogen
Concentration of acid sites 4.7 eq/Kg
Water content 1.5% (H+ form)
Shipped weight610 g/L (38 lbs/ft)
Fines content 0.300 mm: 1.0% max
Surface area45 m2/g
Average pore diameter250 
Swelling
 60 to 70% (dry to Water)
 10 to 15% (dry to hexane)
 10 to 15% (dry to toluene)
 15 to 20% (dry to ethylene dichloride)
 30 to 40% (dry to ethyl acetate)
 60 to 70% (dry to ethyl alcohol, 95%)
 15 to 20% (dry to phenol)
 3 to 5% (dry to benzene)

3.2. General Procedure for the Synthesis of 4-Aryl Substituted 3,4-Dihydropyrimidin-2-(1H)-ones/thiones

A mixture of -diketone (1.0 mmol), aldehyde (1.0 mmol), urea/thiourea (1.2 mmol), and Amberlyst 15 DRY (50 mg) in anhydrous ethanol (10 mL) was refluxed for an appropriate time as indicated by TLC. After completion of the reaction the catalyst was filtered and washed with ethyl acetate until free from organic material. The solvent was evaporated at reduced pressure and obtained solid was crystallized from ethanol to afford pure 3,4-dihydropyrimidin-2-(1 )-ones/thiones 1(a–t) in excellent yields.

3.3. General Procedure for the Synthesis of 3,4-Dihydro-4,6-diphenylpyrimidin-2(1H)-ones

A mixture of acetophenone (1.0 mmol), aldehyde (1.0 mmol), urea (1.5 mmol) and Amberlyst 15 DRY (50 mg) in anhydrous ethanol (10 mL) was refluxed for an appropriate time as indicated by TLC. After completion of the reaction the catalyst was filtered and washed with ethyl acetate until free from organic material. The solvent was evaporated at reduced pressure and the solid obtained was recrystallised from ethanol to afford pure 3,4-dihydro-4,6-diphenylpyrimidine-2(1 )-ones 2(a–f) in excellent yields.

3.4. General Procedure for the Reaction of Cyclohexanone, Aldehydes, and Urea

A mixture of cyclohexanone (1.0 mmol), aldehyde (2.0 mmol), urea (3.0 mmol) and Amberlyst 15 DRY (50 mg) in anhydrous ethanol (10 mL) was refluxed for an appropriate time as indicated by TLC. After completion of the reaction the catalyst was filtered and washed with ethyl acetate until free from organic material. The solvent was evaporated at reduced pressure and the solid obtained was recrystallised from ethanol to afford the desired spirofused heterotricyclic products 3(a–d) in 85–92% yield.

3.5. Spectral Data of Compounds

5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (1a)
Mp 205–207°C; 1HNMR (DMSO- ) : 1.09 (t, 3H,  Hz, OCH2CH3), 2.25 (s, 3H, CH3), 3.97 (q, 2H,  Hz, OCH2), 5.05 (d, 1H, –CH), 7.28 (m, 5H, Ar-H), 7.75 (s, 1H, NH), 9.20 (s, 1H, NH); 13C-NMR (DMSO- ) : 14.11, 17.94, 54.91, 60.05, 100.95, 112.85, 113.05, 125.15, 125.81, 129.05, 131.20, 150.16, 155.47, 163.81; IR ( ; KBr, cm−1): 3240, 1722, 1638; ESI-MS 261 (M + H); C14H16N2O3 (260.29); Calcd. C, 64.60; H, 6.20; N, 10.76; O, 18.44. Found. C, 64.63; H, 6.18; N, 10.73; O, 18.47.

5-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1b)
Mp 202-203°C; 1H-NMR (DMSO- ) : 1.15 (t, 3H,  Hz, OCH2CH3), 2.33 (s, 3H, CH3), 3.78 (s, 3H, –OCH3), 4.06 (q, 2H,  Hz, OCH2CH3), 5.34 (d, 1H, –CH), 6.82 (d, 2H, , Ar-H), 7.22 (d, 2H, , Ar-H), 7.76 (s, 1H, NH), 9.26 (s, 1H, NH); 13C-NMR (DMSO- ) :14.32, 18.80, 55.23, 55.40, 60.17, 101.68, 114.06, 127.97, 136.22, 146.16, 153.59, 159.30, 165.87; IR ( ; KBr, cm−1): 3232, 1720, 1638; ESI-MS 291 (M + H); C15H18N2O4 (290.31); Cacld. C, 62.06; H, 6.25; N, 9.65; O, 22.04. Found. C, 62.08; H, 6.22; N, 9.69; O, 22.02.

5-(Ethoxycarbonyl)-4-(4-dimethylamino-phenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1c)
Mp 254–256°C; 1H-NMR (DMSO- ) : 0.99 (t, 3H,  Hz, OCH2CH3), 2.11 (s, 3H, CH3), 2.84 (s, 6H, N(CH3)2), 4.09(q, 2H,  Hz, OCH2CH3), 5.05 (d, 1H, , –CH), 6.42 (d, 2H, , Ar-H), 7.12 (d, 2H, , Ar-H), 7.15 (s, 1H, NH), 9.05 (s, 1H, NH); 13C-NMR (DMSO- ) : 14.28, 18.78, 44.47, 55.23, 60.15, 101.60, 112.05, 125.65, 134.25, 141.16, 153.46, 159.02, 165.24; IR ( ; KBr, cm−1): 3242, 1721, 1637; ESI-MS 304 (M + H); C16H21N3O3; (303.36); Calcd. C, 63.35; H, 6.98; N, 13.85; O, 15.82. Found. C, 63.38; H, 6.93; N, 13.87; O, 15.79.

5-(Ethoxycarbonyl)-4-(4-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1d)
Mp 212-213°C; 1H-NMR (DMSO- ) : 1.11 (t, 3H,  Hz, OCH2CH3), 2.32 (s, 3H, CH3), 4.03 (q, 2H,  Hz, OCH2CH3), 5.78 (d, 1H, , –CH), 7.51 (d, 2H, , Ar-H), 7.69 (s, 1H, NH), 8.16 (d, 2H, , Ar-H), 9.05 (s, 1H, NH); 13C-NMR (DMSO- ) : 14.22, 18.71, 55.81, 60.15, 101.60, 118.15, 130.37, 138.34, 152.26, 153.41, 159.15, 165.85; IR ( ; KBr, cm−1): 3235, 1740, 1631; ESI-MS 306 (M + H); C14H15N3O5; (305.29); Calcd. C, 55.08; H, 4.95; N, 13.76; O, 26.20. Found. C, 55.10; H, 4.93; N, 13.79; O, 26.16.

5-(Ethoxycarbonyl)-4-(4-chlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1e)
Mp 214-215°C; 1H-NMR (DMSO- ) : 1.12 (t, 3H,  Hz, OCH2CH3), 2.30 (s, 3H, CH3), 3.91 (q, 2H,  Hz, OCH2CH3), 5.70 (d, 1H, , –CH), 7.21 (d, 2H, , Ar-H), 7.69 (s, 1H, NH), 7.94 (d, 2H, , Ar-H), 9.16 (s, 1H, NH); 13C-NMR (DMSO- ) : 14.18, 18.62, 55.72, 60.21, 101.55, 118.17, 130.32, 142.29, 152.31, 153.39, 159.17, 165.83; IR ( ; KBr, cm−1): 3225, 1720, 1615; ESI-MS 295 (M + H); C14H15ClN2O3; Calcd. C, 57.05; H, 5.13; Cl, 12.03; N, 9.50; O, 16.29. Found. C, 57.08; H, 5.10; Cl, 12.06; N, 9.47; O, 16.31.

5-(Methoxycarbonyl)-4-(4-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1f)
Mp 237–239°C; 1H-NMR (DMSO- ) : 2.21 (s, 3H, CH3), 3.90 (s, 3H, –COOCH3), 5.51 (d, 1H, , –CH), 7.42 (d, 2H, , Ar-H), 7.44 (s, 1H, NH), 8.05 (d, 2H, , Ar-H), 9.05 (s, 1H, NH); 13C-NMR (DMSO- ) δ: 18.64, 52.40, 55.40, 109.60, 113.23, 128.31, 137.20, 149.65, 155.45, 160.36, 166.20; IR ( ; KBr, cm−1): 3232, 1724, 1631; ESI-MS 292 (M + H); C13H13N3O5; (291.26); Calcd. C, 53.61; H, 4.50; N, 14.43; O, 27.47. Found. C, 53.64; H, 4.47, N, 14.46; O, 27.44.

5-(Methoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1g)
Mp 192-193°C; 1H-NMR (DMSO- ) : 2.24 (s, 3H, CH3), 3.92 (s, 3H, –COOCH3), 3.75 (s, 3H, –OCH3), 5.22 (d, 1H, –CH), 6.76 (d, 2H, , Ar-H), 7.18 (d, 2H, , Ar-H), 7.62 (s, 1H, NH), 9.15 (s, 1H, NH); 13C-NMR (DMSO- ) δ: 18.61, 53.36, 55.05, 55.87, 108.54, 113.21, 128.47, 137.64, 148.54, 154.16, 160.81, 165.94; IR ( ; KBr, cm−1): 3242, 1721, 1637; ESI-MS 277 (M + H); C14H16N2O4; (276.29); Calcd. C, 60.86; H, 5.84; N, 10.14; O, 23.16. Found. C, 60.89; H, 5.81, N, 10.17; O, 23.13.

5-(Ethoxycarbonyl)-6-methyl-4-styryl-3,4-dihydropyrimidin-2(1H)-one (1h)
Mp 231–233°C; 1H-NMR (DMSO- ) δ: 1.20 (t, 3H,  Hz, OCH2CH3), 2.21 (s, 3H, CH3), 4.09 (q, 2H,  Hz, OCH2CH3), 4.74 (d, 1H, , –CH), 6.20 (dd, , 6.0 Hz, 1H, CH=C–H), 6.37 (d,  Hz, 1H, H–C=CH) 7.21–7.46 (m, 5H, Ar-H), 7.53 (s, 1H, NH), 9.14 (s, 1H, NH); 13C-NMR (DMSO- ) : 14.21, 17.31, 51.84, 59.45, 98.54, 127.34, 128.54, 129.54, 130.59, 131.24, 135.24, 145.34, 153.62, 165.23; IR ( ; KBr, cm−1): 3242, 1704, 1652; ESI-MS 287 (M + H); C16H18N2O3; (286.33); Calcd. C, 67.12; H, 6.34; N, 9.78; O, 16.76. Found. C, 67.15; H, 6.32; N, 9.81; O, 16.73.

5-(Ethoxycarbonyl)-4-(3-nitrophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (1i)
Mp 206-207°C; 1H-NMR (DMSO- ) : 1.15 (t, 3H,  Hz, OCH2CH3), 2.27 (s, 3H, CH3), 4.02 (q, 2H,  Hz, OCH2CH3), 5.81 (d, 1H, , –CH), 7.23–7.37 (m, 4H, Ar-H), 7.78 (s, 1H, NH), 9.34 (s, 1H, NH); 13C-NMR (DMSO- ) : 14.14, 18.60, 55.64, 60.21, 101.34, 126.25, 128.02, 129.32, 130.75, 135.65, 144.34, 160.40, 165.64, 182.65; IR ( ; KBr, cm−1): 3245, 1725, 1632, 1575, 1545; ESI-MS 322 (M + H); C14H15N3O4S; (321.35); Calcd. C, 52.33; H, 4.70; N, 13.08; O, 19.92; S, 9.98. Found. C, 52.36; H, 4.66; N, 13.11; O, 19.88; S, 9.99.

5-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (1j)
Mp 154–156°C; 1H-NMR (DMSO- ) : 1.17 (t, 3H,  Hz, OCH2CH3), 2.37 (s, 3H, CH3), 4.12 (s, 3H, –OCH3), 4.15 (q, 2H,  Hz, OCH2CH3), 5.44 (d, 1H, –CH), 7.11 (d, 2H, , Ar-H), 7.37 (d, 2H, , Ar-H), 7.84 (s, 1H, NH), 9.43 (s, 1H, NH); 13C-NMR (DMSO- ) : 14.32, 18.05, 55.24, 55.49, 60.45, 101.84, 114.32, 127.74, 137.25, 147.15, 159.45, 165.62, 182.48; IR ( ; KBr, cm−1): 3240, 1725, 1635, 1574, 1540; ESI-MS 307 (M + H); C15H18N2O3S; (306.38); Calcd. C, 58.80; H, 5.92; N, 9.14; O, 15.67; S, 10.47. Found. C, 58.84; H, 5.89; N, 9.17; O, 15. 64; S, 10.49.

5-(Ethoxycarbonyl)-4-(3-1H-indole)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1n)
Mp. 212–214°C; 1H-NMR (DMSO- ) : 9.17 (s, 1H, NH), 7.04 (s, 1H, NH), 8.48 (s, 1H, NH), 7.76 (s, 1H), 7.18–7.34 (m, 4H), 5.23 (d, 1H,  Hz), 3.97 (q, 2H,  Hz), 2.24 (s, 3H), 1.15 (t, 3H,  Hz); 13C-NMR (DMSO- ) : 172.10, 155.25, 152.90, 136.90, 127.30, 123.20, 121.80, 119.10, 118.90, 111.15, 106.90, 104.35, 60.10, 34.15, 14.90, 13.90. IR ( ; KBr, cm−1): 3417, 3356, 3240, 2978, 1702, 1653, 1538, 1187, 1085, 870; ESI-MS 300 (M + H); C16H17N3O3; (299.32); Calcd: C, 64.20; H, 5.72; N, 14.04; O, 16.04. Found: C, 63.89; H, 5.93; N, 14.37; O, 16.09.

5-(Ethoxycarbonyl)-4-(3-quinoline)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1q)
Mp 245–247°C; 1H-NMR (DMSO- ) : 9.25 (s, 1H, NH), 7.73 (s, 1H, NH), 8.32 (s, 1H), 7.63–7.79 (m, 4H), 7.80 (s, 1H), 5.12 (d, 1H,  Hz), 4.11 (q, 2H,  Hz), 2.28 (s, 3H), 1.09 (t, 3H,  Hz); 13C-NMR (DMSO- ) : 172.50, 155.25, 153.35, 148.10, 147.15, 135.05, 135.05, 129.10, 127.30, 126.45, 126.10, 104.50, 60.10, 53.00, 14.90, 13.90; IR ( ; KBr, cm−1): 3408, 3365, 3280, 1698, 1640, 1513, 1227, 779; ESI-MS 312 (M + H); C17H17N3O3 (311.34); Calcd: C, 65.58; H, 5.50; N, 13.50; O, 15.42. Found: C, 65.63; H, 5.61; N, 13.42; O, 15.37.

5-(Ethoxycarbonyl)-4-(2-pyrimidine)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (1r)
Mp 255–257°C; 1H-NMR (DMSO- ) : 9.20 (s, 1H, NH), 7.65 (s, 1H, NH), 8.42 (d, 2H,  Hz), 7.38 (t, 1H,  Hz), 5.10 (d, 1H,  Hz), 4.02 (q, 2H,  Hz), 2.23 (s, 3H), 1.11 (t, 3H,  Hz); 13C-NMR (DMSO- ) : 172.60, 168.70, 157.20, 155.85, 153.85, 119.90, 104.20, 60.10, 56.10, 15.15, 13.90; IR ( ; KBr, cm−1): 3413, 3385, 3245, 2965, 1709, 1658, 1540, 1235, 1090, 780; ESI-MS 263 (M + H); C12H14N4O3; (262.26); Calcd: C, 54.96; H, 5.38; N, 21.36; O, 18.30. Found: C, 54.84; H, 5.29; N, 22.04; O, 18.75.

5-(Ethoxycarbonyl)-4-(4-hydroxyl-2H(1)-benzopyran-2-one-3-yl)-6-methyl-3,4-dihydropyrimi din-2(1H)-one (1t)
277–279°C; 1H-NMR (DMSO- ) : 11.85 (s, 1H, OH), 9.80 (s, 1H, NH), 7.69 (s, 1H, NH), 7.30–7.80 (m, 4H), 4.85 (d, 1H,  Hz), 4.23 (q, 2H,  Hz), 2.35 (s, 3H), 1.21 (t, 3H,  Hz); 13C-NMR (DMSO- ) : 172.50, 171.20, 164.15, 155.10, 153.60, 152.20, 131.15, 129.80, 122.30, 121.10, 117.80, 116.25, 94.50, 60.20, 43.25, 15.15, 14.15; IR ( ; KBr, cm−1): 3389, 3240, 2943, 1721, 1705, 1619, 1562, 1235, 1123, 810; ESI-MS 345 (M + H); C17H16N2O6; (344.32); Calcd: C, 59.30; H, 4.68; N, 8.14; O, 27.88. Found: C, 59.24; H, 4.76; N, 8.07; O, 28.01.

4,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one (2a)
Mp 233–236°C; 1H-NMR (DMSO- ) : 9.51 (s, 1H, NH), 9.21 (s, 1H, NH), 7.21–7.62 (m, 10H, Ar-H), 5.20 (d, 1H,  Hz, C=CH), 5.12 (d, 1H,  Hz, CH); 13C-NMR (DMSO- ) : 150.2, 143.2, 136.6, 134.2, 128.6, 126.4, 128.7, 126.9, 97.5, 51.9; IR ( ; KBr, cm−1): 3312, 1685, 1598, 1449; ESI-MS 251 (M + H); C16H14N2O; (250.30); Calcd. C, 76.78; H, 5.64; N, 11.19; O, 6.39. Found. C, 76.53; H, 5.34; N, 11.02; O, 6.13.

4-(4-chlorophenyl)-6-phenyl-3,4-dihydropyrimidin-2(1H)-one (2b)
Mp 267–269°C; 1H-NMR (DMSO- ) : 9.42 (s, 1H, NH), 9.12 (s, 1H, NH), 7.19–7.78 (m, 9H, Ar-H), 5.60 (d, 1H,  Hz, C=CH), 5.01 (d,1H,  Hz, CH); 13C-NMR (DMSO- ) : 150.2, 141.3, 136.6, 134.2, 132.3, 128.6, 128.3, 128.7, 126.4, 97.5, 51.9; IR ( ; KBr, cm−1): 3319, 1683, 1569, 1463; ESI-MS 285 (M + H); C16H13ClN2O3; (284.74); Calcd. C, 67.49; H, 4.60; Cl, 12.45, N, 9.84, O, 5.62. Found. C, 67.18; H, 4.24; Cl, 12.21; N, 9.32, O, 5.41.

4-(4-methoxyphenyl)-6-phenyl-3,4-dihydropyrimidin-2(1H)-one (2d)
Mp 259–261°C; 1H-NMR (DMSO- ) : 9.23 (s, 1H, NH), 8.87 (s, 1H, NH), 7.18–7.56 (m, 9H, Ar-H), 5.85 (d, 1H,  Hz, C=CH), 5.26 (d, 1H,  Hz, CH), 3.69 (s, 3H, OCH3); 13C-NMR (DMSO- ) : 158.6, 150.2, 136.6, 135.5, 134.2, 127.9, 114.1, 128.7, 128.0, 126.4, 97.5, 55.8, 51.9; IR ( ; KBr, cm−1): 3345, 1645, 1536, 1422; ESI-MS 281 (M + H); C17H16N2O2; (280.32); Calcd. C, 72.84; H, 5.75, N, 9.99; O, 11.42. Found. C, 72.53; H, 5.42; N, 9.73; O, 11.19.

4,8-diphenyloctahydro-1H-pyrimido[5,4-i]quinazoline-2,10(3H,11H)-dione (3a)
Mp 327–329°C; 1H-NMR (DMSO- ) : 7.40–7.19 (m, 10 H), 7.08 (s, 1H), 6.97 (s, 1H), 6.62 (s, 1H), 6.39 (s, 1H), 4.50 (d, 1H), 4.82 (d, 1H), 2.02 (m, 2H), 1.38 (m, 2H), 1.24 (m, 2H), 0.82 (t, 2H); 13C-NMR (DMSO- ) : 155.9, 140.5, 128.1, 128.6, 126.0, 63.7, 50.2, 49.1, 17.8; ESI-MS 377 (M + H); C22H24N4O2; (376.45); Calcd. C, 70.19; H, 6.43; N, 14.88; O, 8.50. Found. C, 70.03; H, 6.21; N, 14.45; O, 8.23.

4,8-bis(2-chlorophenyl)octahydro-1H-pyrimido[5,4-i]quinazoline-2,10(3H, 11H)-dione (3d)
Mp 321–323°C; 1H-NMR (DMSO- ) : 7.42 (s, 1H), 7.35–7.10 (m, 9H), 6.75 (s, 1H), 5.32 (s, 1H), 5.32 (s, 1H), 3.91 (m, 3H), 3.69 (m, 3H), 2.30 (m, 2H), 2.01 (m, 1H), 1.84 (m, 1H), 1.32 (m, 1H), 1.19 (m, 1H), 0.89 (m, 1H); 13C-NMR (DMSO- ) : 155.9, 140.5, 133.4, 129.5, 128.6, 127.4, 63.7, 48.6, 45.1, 23.6, 17.8; ESI-MS 445 (M + H); C22H22Cl2N4O2 (445.34); Calcd. C, 59.33; H, 4.98; Cl, 15.92; N, 12.58; O, 7.19. Found. C, 59.12; H, 4.56; Cl, 15.74; N, 12.28; O, 7.02.

4. Conclusion

In conclusion, we have developed a simple, efficient, environmentally benign, and improved protocol for the synthesis of 3,4-dihydropyrimidin-2(1 )-ones/thiones over Amberlyst 15 DRY as the catalyst with excellent yields. The simplicity of the system, ease of separation/reuse of the catalyst due to its heterogeneous nature, excellent yields of the products, and ease of workup fulfill the triple bottom line philosophy of green chemistry and make the present methodology environmentally benign.

Conflict of Interests

S. R. Jetti declares that there is no conflict of interests.

Acknowledgments

One of the authors (S. R. Jetti) is grateful to Madhya Pradesh Council of Science and Technology (MPCST), Bhopal, for the award of fellowship. The authors are also thankful to Deputy Director and Head, SAIF, Central Drug Research Institute (CDRI), Lucknow, for providing spectral data and the Department of Chemistry, Vikram University, Ujjain, for extending laboratory facilities and IR data.

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Copyright © 2012 Srinivasa Rao Jetti et al. 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.


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