1 Introduction

The gradually increasing demand for greener methodology for concurrent chemical synthesis has enforced chemists to develop atomic economically and environmentally benign synthetic routes for producing well usable chemicals.1 Visible-light-assisted transformations have especially attracted growing interest due to their green and beneficial properties, sustainability, readily availability and ease of handling.2 In addition, compared to the conventional catalytic protocols, photo-catalysis under visible-light irradiation has been revealed as a powerful synthetic tool that produces mild and eco-friendly organic conversions.3,4,5,6 Exhilarate by this, various dyes and metal-complexes; bearing ruthenium and iridium, are reported as photocatalysts in the last couple of years especially.7,8,9,10,11,12,13,14,15,16

The controlled oxidation of alcohols is one of the important transformations in organic synthetic chemistry as their products play an important intermediate role in the formation of fine chemicals, important agrochemicals, pharmaceutical entities and other high-value products.17,18,19 Oxidation of primary aromatic alcohols are mostly achieved using rather strong oxidizing agents, that are toxic and hazardous to the environment i.e. hyperchlorite, permanganate, etc. and expensive noble metal catalysts including Au, Pt, Pd.20,21,22,23,24,25 As the alternative route, oxygen plays an important role as an excellent oxidant because of prevention of toxic, hazardous and stoichiometric by-products.26 Based on the perspective, various homogenous and heterogeneous metal catalysts have been reported. In equality, transition-metal free photocatalysts are greener and striking, because of inexpensive, easy departure from the reaction mixture and non-poisonous.27,28 So far, several photocatalytic methods have also been reported for the oxidation of primary aromatic alcohols.29,30,31,32,33,34

Notably, 3,4-dihydropyrimidin-2(1H)-one (DHPMs) are the core structural motifs for many potentially active biological molecules such as calcium channel blockers, ant-inflammatory and antitumor.35 DHPMs are identified as encouraging anticancer agents (Figure 1) especially monastrol, responsible to block the bipolar-mitotic-spindle in mammalian cells that results in triggering the arrest of G2/M mitotic phase further leading to cell apoptosis.36,37

Figure 1
figure 1

Some DHPM derivatives with anticancer activity.

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Various methods have been published in the literature for the composite of 3,4-dihydropyrimidinones by using ultrasonic irradiation, microwaves, ionic liquids, Thermal methods and metal catalysts (i.e. copper (II) sulfamate, Dendrimer-PWA).38,39,40,41,42,43,44,45,46,47,48 These methods and catalysts mentioned above have the common drawbacks of difficult work-up, lower product yield, noxious and steep catalysts, acidic circumstance and long-time reactions.49

The reported literature prompted us to explore a tandem cascade methodology for the fabrication of DHPMs utilizing primary aromatic alcohols. For a tandem cascade approach, a photooxidative system is required to be established that is selective and high yielding.

Here, we developed a greener and environmentally benign protocol for the synthesis of 3,4-DHPMs using molecular oxygen,28,50,51,52 visible light irradiation as a green energy source,53 eosin Y as photoreceptor and sensitizer, silver nitrate as an add-on photoreaction enhancer and inorganic salt K2S2O8 as a strong oxidizing agent.54 Eosin Y revealed unique properties like as rapid intersystem crossing to the lowest triplet state, high photo and chemical stability, ease of separation from the reaction mixture and high catalytic efficiency.55 This strategy embraces two distinct features involving activation of the system using visible light and initial activation of the dye through light absorption followed by system activation. Our investigated style has a prominent quality like easy workup, inexpensive catalyst, simple filtration, high yield and easy scalability. Our approach combines a dye i.e. Eosin Y, a light energy acceptor, with an electron acceptor photocatalyst, silver nitrate.

2 Experimental

2.1 General information and materials

General standard methods were used to purify and dry the solvents. Reagents and solvents (procured from Spectrochem, Aldrich, Acros and Merck) were used as such without added purification unless otherwise required. TLC (Analytical thin layer chromatography) was performed on Merck Kieselgel-60 F-254. Silica-gel 100-200 mesh was used to perform column chromatography. M.P. (Melting points) were recorded on Mel-Temp apparatus in capillary tubes and are uncorrected. Proton NMR spectra were attained at Bruker spectrometer (400 MHz) using CDCl3 as solvent (7.26 ppm- referenced to residual chloroform) or d6-DMSO (2.50 ppm – referenced to residual and 3.34 ppm – referenced to residual water in DMSO-d6). Chemical shift values are articulated in ppm (parts per million) downfield with respect to TMS. Coupling constant values (J values) are presented in Hz. 13C NMR spectra were obtained at 75 MHz in using Bruker spectrometers using CDCl3 as solvent (77.0 ppm – referenced to residual chloroform) or d6-DMSO (39.5 ppm – referenced to residual DMSO). Perkin Elmer (Spectrum-II) used for IR spectra. Mass spectrophotometer (Brucker-micrOTOF-QII) used for mass spectra.

2.2 Experimental procedures

2.2.1 General procedure of the synthesis of 3,4-dihydropyrimidin-2(1H)-ones

Alcohol 1b (1.0 mmol), α-ketoester 2b (1.0 mmol) and urea 3b (1.2 mmol) was dissolved in a mixture of acetonitrile and water (1:1) at room temperature in the presence of air bubble. Eosin Y (1.0 mmol), Silver nitrate (2.0 mol%) and potassium persulphate (1.0 mmol) was added and the reaction mixture was stirred for 48 h under visible light at room temperature. The reaction was monitored using TLC. After the completion of reaction, the reaction mixture was partitioned between water and ethyl acetate. The separated organic layer was washed with saturated brine solution, dried over anhydrous sodium sulfate, concentrated in vacuo to afford compounds DHPM with excellent yields (upto 88%). The compounds DHPM were further purified by using column chromatography over silica gel with the mixture of ethylacetate/hexane to get the pure DHPMs.


Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4a: Yield 88%; white solid, M.p. 203–204 °C; IR (ATR) ν cm−1 3243 (N-H), 1701 (C=O), 1638 (C=C). 1H NMR (400 MHz, DMSO-d6) δ 9.22 (1H, s, NH), 7.75 (1H, s, NH), 7.27 (5H, m, ArH), 5.15 (1H, d, J = 4.0 Hz, CH), 3.98 (2H, q, J = 15.2, 8.0 Hz, CH2), 2.26 (3H, s, CH3), 1.10 (3H, t, J = 8.0 Hz, CH3); 13C NMR (75 MHz, DMSO-d6) δ 165.9, 153.1, 148.3, 145.3, 129.1, 128.2, 127.8, 98.2, 60.2, 55.5, 19.0, 14.7. MS m/z 261 (M+1); Anal. Calc. for C14H16N2O3: C, 64.60; H, 6.20; N, 10.76; found: C, 64.59; H, 6.23; N, 10.73.


Methyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4b: Yield 80%; White solid; M.p. 208–210 °C; IR (ATR) ν cm−1 3228 (N-H), 1697 (C=O), 1653 (C=C).1HNMR (400 MHz, DMSO-d6) δ 9.20 (1H, s, NH), 7.70 (1H, s, NH), 7.29 (5H, m, ArH), 5.13 (1H, d, J = 4.0 Hz, CH), 3.70 (s, OCH3), 2.28 (3H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 164.3, 152.7, 148.9, 145.1, 128.9, 128.2, 127.5, 100.2, 55.6, 54.1, 15.7. MS m/z247 (M+1); Anal. Calc. for C13H14N2O3: C, 63.40; H, 5.73; N, 11.38; found: C, 63.42; H, 5.76; N, 11.33.


Ethyl 4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4c: Yield 75%; white solid; M.p. 213-215 °C; IR (ATR) ν cm−1 3239 (N-H), 1701 (C=O), 1638 (C=C).1H NMR (400 MHz CDCl3) δ 7.98 (s,1H, NH), 5.81 (s, 1H, NH), 7.27-7.33 (m, 4H, ArH), 5.41 (s, 1H, CH), 4.10 (2H, q, CH2), 2.38 (3H, s, CH3), 1.21 (3H, t, CH3); 13C NMR (75MHz, CDCl3) δ 165.4, 153.0, 146.3, 142.1, 133.7, 128.9, 128.0,101.1, 60.2, 55.17, 18.7; MS m/z 296 (M+2); Anal. Calc. for C14H15ClN2O3: C, 57.05; H, 5.13; N, 9.50; found: C, 57.04; H, 5.18; N, 9.42.


Methyl 4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4d: Yield 73%; white solid; M.p. 180-181 °C; IR (ATR) ν cm−1 3225 (N-H), 1706 (C=O), 1635 (C=C).1H NMR (400 MHz DMSO-d6) δ 9.30 (s,1H, NH), 7.72 (s, 1H, NH), 7.39 (m, 4H, ArH), 5.12 (s, 1H, CH), 3.59 (s, 3H, OCH3), 2.25 (s, 3H, CH3); 13C NMR (75MHz, DMSO-d6) δ 165.3, 152.8, 149.5, 132.8, 132.3, 129.5, 128.4, 128.0, 127.7, 98.9, 51.5, 51.4, 18.7; MS m/z 282 (M+2); Anal. Calc. for C13H13ClN2O3: C, 55.62; H, 4.67; N, 9.98; found: C, 55.64; H, 4.71; N, 9.94.


Ethyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4e: Yield 85%; light brown solid; M.p. 205-206 °C; IR (ATR) ν cm−1 3227 (N-H), 1705 (C=O), 1643 (C=C).1H NMR (400 MHz, DMSO-d6) δ 10.11 (s, 1H, NH), 8.30 (s, 1H, NH), 7.30 (m, 2H, ArH), 6.79 (m, 2H, ArH), 5.25 (s, 1H, CH), 3.95 (2H, q, J = 16.0, 8.0 Hz, CH2), 3.84 (s, 3H, Ar-OCH3), 2.30 (3H, s, CH3), 1.09 (3H, t, J = 8.0 Hz, CH3). 13C NMR (75MHz, DMSO-d6) δ 165.6, 160.5, 153.8, 134.5, 127.9, 113.8, 106.6, 55.8, 52.5, 52.9, 19.3; MS m/z291 (M+1); Anal. Calc. for C15H18N2O4: C, 62.06; H, 6.25; N, 9.65; found: C, C, 62.08; H, 6.28; N, 9.60.


Methyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4f: Yield 82%; light brown solid; M.p. 187-188 °C; IR (ATR) ν cm−1 3226 (N-H), 1708 (C=O), 1653 (C=C). 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H, NH), 8.57 (s, 1H, NH), 7.36 (m, 2H, ArH), 6.83 (m, 2H, ArH), 5.28 (s, 1H, CH), 3.83 (s, 3H, Ar-OCH3), 3.45 (s, 3H, OCH3), 2.30 (s, 3H, CH3). 13C NMR (75MHz, DMSO-d6) δ 166.0, 160.8, 154.2, 134.8, 127.4, 113.2, 106.5, 56.5, 51.8, 51.2, 19.9; MS m/z 277 (M+1); Anal. Calc. for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14; found: C, 60.90; H, 5.81; N, 10.10.


Ethyl 6-methyl-2-oxo-4-(p-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4g: Yield 78%; light brown solid; M.p. 209-210 °C; IR (ATR) ν cm−1 3241 (N-H), 1700 (C=O), 1641 (C=C).1H NMR (400 MHz, DMSO-d6,) δ 10.36 (s, 1H, NH), 8.47 (s, 1H, NH), 7.20 (m, 2H, ArH), 6.72 (m, 2H, ArH), 5.31 (s, 1H, CH), 3.91 (2H, q, J = 16.0, 8.0 Hz, CH2), 2.32 (3H, s, CH3), 2.21 (s, 3H, Ar-CH3), 1.11 (3H, t, J = 8.0 Hz, CH3); 13C NMR (75MHz, DMSO-d6) δ 165.2, 152.7, 151.1, 139.9, 134.7, 129.9, 128.5, 107.7, 53.9, 51.7, 21.0, 19.1; MS m/z275 (M+1); Anal. Calc. for C15H18N2O3: C, 65.68; H, 6.61; N, 10.21; found: C, 65.70; H, 6.66; N, 10.19.


Methyl 6-methyl-2-oxo-4-(p-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4h: Yield 80%; light brown solid; M.p. 214-215 °C; IR (ATR) ν cm−1 3245 (N-H), 1703 (C=O), 1632 (C=C).1H NMR (400 MHz, DMSO-d6,) δ 10.50 (s, 1H, NH), 8.35 (s, 1H, NH), 7.01 (m, 4H, ArH), 5.20 (s, 1H, CH), 3.54 (s, 3H, OCH3), 2.28 (s, 3H, CH3), 2.24 (s, 3H, Ar-CH3); 13C NMR (75MHz, DMSO-d6) δ 165.3, 152.2, 151.0, 139.6, 134.0, 129.2, 128.4, 107.0, 53.3, 51.5, 21.7, 19.5; MS m/z 261 (M+1); Anal. Calc. for C14H16N2O3: C, 64.60; H, 6.20; N, 10.76; found: C, 64.53; H, 6.23; N, 10.68.


Ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4i: Yield 82%; white solid; M.p. 230-232 °C; IR (ATR) ν cm−1 3229 (N-H), 1706 (C=O), 1639 (C=C).1H NMR (400 MHz DMSO-d6) δ 9.53 (s,1H, NH), 7.84 (s, 1H, NH), 7.13 (m, 2H, ArH), 6.79 (m, 2H, ArH), 5.10 (s, 1H, CH), 3.87 (2H, q, J = 16.0, 8.0 Hz, CH2), 2.28 (3H, s, CH3), 1.07 (3H, t, J = 8.0 Hz, CH3); 13C NMR (75MHz, DMSO-d6) δ 165.1, 152.7, 149.8, 132.4, 132.8, 129.7, 128.1, 128.0, 127.7, 98.7, 51.7, 51.4, 18.9; MS m/z277 (M+1); Anal. Calc. for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14; found: C, 60.88; H, 5.94; N, 10.08.


Methyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4j: Yield 80%; white solid; M.p. 240-242 °C; IR (ATR) ν cm−1 3231 (N-H), 1704 (C=O), 1636 (C=C).1H NMR (400 MHz DMSO-d6) δ 9.43 (s,1H, NH), 7.77 (s, 1H, NH), 7.00 (m, 4H, ArH), 5.08 (s, 1H, CH), 3.60 (s, 3H, OCH3), 2.27 (s, 3H, CH3); 13C NMR (75MHz, DMSO-d6) δ 166.5, 152.9, 149.8, 132.5, 132.4, 129.7, 128.9, 128.4, 127.8, 98.7, 51.7, 51.6, 18.6; MS m/z263 (M+1); Anal. Calc. for C13H14N2O4: C, 59.54; H, 5.38; N, 10.68; found: C, 59.55; H, 5.47; N, 10.60.


Ethyl 6-methyl-2-oxo-4-propyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4k: Yield 5%; White solid; M.p. 154-156 °C IR (ATR) ν cm−1 3246 (N-H), 1708 (C=O), 1632 (C=C).1HNMR (400 MHz, CDCl3) δ7.65 (1H, s, NH), 5.60 (1H, s, NH), 4.25 (1H, t, CH), 4.11 (2H, q, CH2), 2.22 (3H, s, CH3), 1.64 (4H, m, CH2-CH2), 1.21 (t, 3H, -CH3), 0.85 (t, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ165.9, 154.2, 146.5, 101.7, 59.9, 51.4, 39.1, 18.6, 17.6, 14.3.MS m/z227 (M+1); Anal. Calc. for C11H18N2O3: C, 58.39; H, 8.02; N, 12.38; found: C, 58.43; H, 8.14; N, 12.31.


Ethyl 4-ethynyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4l: Yield 22%; White solid; IR (ATR) ν cm−1 3247 (N-H), 1705 (C=O), 1635 (C=C).1HNMR (400 MHz, DMSO-d6) δ 9.30 (1H, s, NH), 7.69 (1H, s, NH), 5.03 (1H, s, CH), 3.90 (2H, q, J = 16.0, 8.0 Hz, CH2), 3.16 (1H, s, CH), 2.27 (3H, s, CH3), 1.25 (t, 3H, -CH3); 13C NMR (75 MHz, DMSO-d6) δ 167.1, 150.4, 147.9, 106.5, 81.1, 72.9, 65.7, 45.2, 17.4, 15.1. MS m/z209 (M+1); Anal. Calc. for C10H12N2O3: C, 57.68; H, 5.81; N, 13.45; found: C, 57.66; H, 5.85; N, 13.39.


Ethyl 4-(3-nitrophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, 4m: Yield 72%; yellow solid; M.p. 228-230 °C; IR (ATR) ν cm−1 3333 (N-H), 1707 (C=O), 1621(C=C).1H NMR (400 MHz DMSO-d6) δ9.38 (s,1H, NH), 8.16 (s, 1H, NH), 7.6-8.10 (m, 4H, ArH), 5.31 (s, 1H, CH), 4.0 (2H, q, CH2), 2.28 (3H, s, CH3), 1.11 (3H, t, CH3); 13C NMR (75MHz, DMSO -d6) δ165.5, 152.2, 149.9, 148.2, 147.4133.4, 130.7, 122.8, 121.4,98.8, 59.8, 54.0, 18.3, 14.4.

3 Results and Discussion

The exploration was started by performing the reaction of benzyl alcohol (1a), ethyl acetoacetate (2a), urea (3a) and K2S2O8 (1 eq.) in acetonitrile/water (1:1) mixture under an open atmosphere and in a dark place at room temperature. The entire substrate was unreacted (Table 1, entry 1) and did not proceed at all even after 48 h. The above testing reaction was also performed at an elevated temperature of 50 °C but could not enhance the result of the reaction. The above test reaction was further studied in the presence of silver nitrate which does not afford any product (Table 1, entry 2). Silver nitrate was replaced with silver acetate and TiO2 but the formation of the product may not be realized (Table 1, entry 3). Following, we examined a similar investigation in visible light (source: white LED bulb), which enabled the formation of traces of the final product on spending 48 h with 1a (Table 1, entry 4). Besides, a similar model reaction was conducted using Eosin Y as photocatalyst (1 mol%), which provided the synthesis of desired 3,4-DHPM 4a was obtained in 48 h with 45% yield under photoreaction (Table 1, entry 5). The characterization of 4a was furnished by 1H NMR, 13C NMR, Mass-Spectrum and IR spectral studies, and found to be matched identically with the previously reported compounds.

Table 1 Optimization of reaction conditions.
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The above outcome was extremely encouraging, for further optimization of the reaction to get an elevated yield of required product 4a. Subsequently, the template reaction was executed by varying amounts of photocatalyst Eosin Y, which does not improve the yield of the wanted product 4a (Table 1, entry 6). We used an organic dye Eosin Y as a photo-catalyst to initiate the reaction, which leads to the dehydrogenation of alcohol into desired carbonyl compound.53 Eosin Y worked as photocatalyst in the reaction. Then, we performed the reaction with varying amounts of K2S2O8 which revealed a decline in the yield of the desired product 4a (Table 1, entries 7 & 8). Potassium persulphate (K2S2O8) used in this protocol is not a photocatalyst, but photolysis of S2O82− to generate sulphate radical anion (SO4. −), which acts as a strong oxidizing agent in an aqueous system.54 The activity of K2S2O8 also depends on the amount of K2S2O8 used in the reaction. The reaction with a high amount of K2S2O8 reduced the desired yield by over-oxidation of alcohol into a carboxylic acid.

To improve the effectiveness of this reaction, we examined the altering amount of AgNO3 commencing 1.0 to 3.0 mol % (Table 1, entries 9-11). It was detected that 2.0 mol % was found as the best possible protocol, which facilitated the yield of the avidity product 4a to 88% in 40 h (Table 1, entry 10). Further increase in the quantity of silver nitrate could not get better yield (Table 1, entry 11). Silver nitrate helps in increasing the oxidation in reaction.56 The role of silver is to activate the molecular oxygen by adsorbing on their surface. It also enhanced the efficiency of eosin Y under the aqueous phase.57,58,59

Afterwards, we carefully evaluated the model reaction with different solvent systems such as DMSO, ethanol, H2O, chloroform, CH3CN and found that the CH3CN/H2O mixture was the most suitable solvent for this reaction as it increases the yield to 88% (Table 1, entries 12-16). Acetonitrile is a good solvent for photo-oxidation.60 It does not only possess strong polarity but also have a good dissolvent capacity of oxygen. To find out the impact of other photocatalysts, we examined the model reaction with different organic photocatalysts (Table 1, entries 17 & 18), which did not enhance the yield of the product.

Hence, the evaluated eosin Y (1.0 mol %), K2S2O8 (1.0 equiv.), AgNO3 (2.0 mol %) were the best choices with visible light irradiation at room temperature under an oxygen atmosphere.

With the optimized reaction conditions in hand, the substrate coverage of this photocatalytic oxidation system was explored (Scheme 1). Based on our initial efforts to obtain the high efficiency of photocatalytic conversion into the desired product, different primary aromatic and aliphatic alcohols were evaluated (Table 2). All the substituted benzyl alcohols with electron-donating and electron-withdrawing groups were easily utilized in this cascade approach in getting substituted 3,4-DHPMs in high yields (Table 2, compound 4a-4j, 4m). Electron-releasing substituents at para, position on the phenyl group were found to be efficient in accelerating the reaction, while electron-withdrawing groups substituents at meta and para position on phenyl group needed longer reaction times for their optimized conversions. Compared with the primary aromatic alcohols, primary aliphatic alcohols are found to be very less reactive.

Scheme 1
scheme 1

Synthesis of various derivatives of 3,4-dihydropyrimidin-2(1H)-ones.

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Table 2 Synthesis of 3,4-dihydropyrimidin-2(1H)-ones (DHPM) (Scheme 1)a.
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We evaluated various derivatives by using different types of primary alcohol (Benzyl alcohol, 4-chlorobenzyl alcohol, propargyl alcohol, methanol and butanol etc.) and α-ketoester (ethyl acetoacetate and methyl acetoacetate) in the reaction (Scheme 1). We used benzyl alcohol with ethyl acetoacetate and urea under similar reaction conditions, which gave 88% yield (4a) and reaction accomplished in 48 h (entry 1, Table 2).

Further benzyl alcohol treated with methyl acetoacetate and reaction conditions remained same which obtained 80% yield of the product (4b) in 48 h (entry 2, Table 2). We also found that both methyl acetoacetate and ethyl acetoacetate under similar optimized conditions gave good to excellent yields between 73-88% with aromatic alcohols (Table 2, entries 4c-4j, 4m). Further, we also treated aliphatic alcohols under similar reaction condition with ethyl acetoacetate that yielded in poor (Table 2, entries 4k-4l) even after an extended duration of time up to 72 h.

A plausible mechanism has been proposed for the in-situ oxidation of alcohol and the formation of 3,4-DHPMs which is summarized in Scheme 2. The sulphate radical anion (SO4. −) acts as an oxidizing agent under photo-irradiative conditions.54,67 It accepts one electron from 3EY* forming sulphate anion (SO42−) and converts it into radical cation (EY+.) Subsequently, EY+• accepts an electron from benzyl alcohol (1b) to regenerate EY and produce benzyl alcohol radical cation (5, Scheme 2). Further, benzyl alcohol radical (6) is formed due to the removal of a proton from 5.53 The Ag(I) activates the molecular oxygen (O2) and transforms it into radical anion (O2−.)58 that further accepts proton form superoxide radical (.OOH). The .OOH transforms 6 into carbonyl compound (7) (Scheme 2).17

Scheme 2
scheme 2

Proposed mechanism step-I in-situ oxidation of primary alcohol.

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The eosin Y gets involve in both the reductive and oxidative quenching cycles.68,69 The eosin Y activates both 7 and β-keto ester (2b) by donating and accepting one electron respectively. The activated aldehyde (8) further interacts with urea to form imine (11) and releases a molecule of H2O. The activated β-keto ester (9) attacks on imine (11) to form 3,4-DHPM by releasing water molecule (Scheme 3).47,70

Scheme 3
scheme 3

Proposed mechanism step-II formation of 3,4-DHPMs.

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4 Conclusions

We have disclosed a robust, efficient, and domino multicomponent cascade novel protocol to design 3,4-dihydropyrimidin-2(1H)-one derivative utilizing Biginelli reaction of primary alcohols using visible-light as green energy source. The key features of the present protocol include the capability to allow an operational simplicity, readily available substrates, straightforward workup, and high yields of the products. The synthetic efficacy and practicality of this Eosin Y based photocatalytic approach can allow in capacitating conventional metal-catalyzed reactions and could be rousing towards functionalization of a broad variety of C-C, and C-N bonds in a sustainable manner.