| 65% |
With potassium carbonate In acetone for 4h; Reflux; |
1 4.1.6 General procedures for the preparation of compounds 3a-t
General procedure: A mixture of 2a-c/2e (5.0mmol) with suitable α,ω-dibromoalkanes (50mmol) and anhydrous K2CO3 (1.4g, 10mmol) in acetone (15mL) was refluxed under stirring for 4h. After cooling, the reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography with hexane/acetone (20:1) as eluent to give compounds 3a-t as white solid. |
| 56.32% |
Stage #1: 7-hydroxy-2H-chromen-2-one With potassium carbonate; triethylamine In acetone at 20℃; for 0.5h;
Stage #2: ethylene dibromide In acetone at 60℃; for 24h; |
The procedure for the synthesis of intermediate coumarin bromides A1-A6
General procedure: For example, to a solution of 7-hydroxycoumarin (5.0 g, 31.0 mmol) in acetone (60.0 mL) was added anhydrous K2CO3 (6.9 g, 50.0 mmol) and triethylamine (1.0 mL) at room temperature. After stirring at room temperature for 30 min, 1, 2-dibromoethane (12.6 g, 62.0 mmol) was added to the reaction mixture, and the whole was refluxed at 60°C for 24 h. Then the reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. The residue was treated with water (200.0 mL) and extracted with dichloromethane (4×200.0 mL). The organic layer was combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified via silica gel column chromatography with mixed petroleum ether and ethyl acetate (5:1, v/v) as eluent, and resulted in a white solid.Compound A1. Yield 56.32%. 1H NMR (500 MHz, CDCl3) δ 7.64-7.63 (d, 1H, J = 9.5 Hz), 7.40-7.39 (d, 1H, J = 8.6 Hz), 6.88-6.86 (dd, 1H, J = 8.6, 2.4 Hz), 6.82-6.81 (d, 1H, J = 2.4 Hz) 6.28-6.27 (d, 1H, J = 9.5 Hz), 4.36-4.34 (t, 2H), 3.69-3.66 (t, 2H). 13C NMR (126 MHz, CDCl3) δ 161.31, 161.15, 155.90, 143.40, 129.09, 113.71, 113.21, 112.97, 101.84, 68.12, 28.54. ESI-MS (m/z): 269.15 ([M]+). |
| 55.18% |
Stage #1: 7-hydroxy-2H-chromen-2-one With potassium carbonate; triethylamine In acetone at 20℃; for 0.5h;
Stage #2: ethylene dibromide In acetone at 60℃; |
1.1.1.The procedure for the synthesis of intermediate coumarin bromides1-4
The intermediate coumarin bromides 1-4 were synthesized as reported in aprevious study.45 The synthetic route is shown in Scheme 1. For example, to a solution of 7-hydroxycoumarin(10.0 g, 62 mmol) in acetone (120 mL) was added anhydrous K2CO3(13.8 g, 100 mmol) and triethylamine (2 mL) at room temperature. After stirringat room temperature for 30 min, 1, 2-dibromoethane (23.29 g, 124 mmol) wasadded to the reaction mixture, and whole was refluxed at 60 °C for 24 h. The precipitate was filtered off and washed withacetone (4×100 mL). The solvent was evaporated under reducedpressure, and the residue was treated with water (100 mL) and extracted withdichloromethane (4×200 mL). The organic layer werecombined, dried with anhydrous Na2SO4, and concentratedunder reduced pressure. The crude product was purified via silicagel column chromatography with mixed petroleum ether and ethyl acetate (5:1,v/v) as eluent, and resulted in a white solid. Compound1.Yield 55.18%. 1H NMR(500 MHz, CDCl3) δ 7.65-7.64(d, 1H, H-4, J=9.5 Hz), 7.41-7.39 (d,1H,H-5, J=8.6 Hz), 6.89-6.86(dd,1H,H-8, J=8.6, 2.4 Hz), 6.82-6.81(d,1H,H-6, J= 2.4 Hz) 6.28-6.27(d,1H,H-3, J=9.5 Hz), 4.37- 4.34(t,2H,H-1’),3.69-3.66(t,2H,H-2’). 13C NMR (126 MHz, CDCl3) δ 161.32,161.13, 155.91, 143.40, 129.09, 113.71, 113.21, 112.97, 101.84, 68.34, 28.54.ESI-MS m/z: 269.15 ([M]+). |
| 55.18% |
Stage #1: 7-hydroxy-2H-chromen-2-one With potassium carbonate; triethylamine In acetone at 20℃; for 0.5h;
Stage #2: ethylene dibromide In acetone at 60℃; for 24h; |
1.1.2. The procedure for the synthesis of intermediatecoumarin bromides1-5
The intermediate coumarin bromides1-5were synthesized as reported in a previous study. The synthetic route is shown in Scheme 1.For example,to a solution of 7-hydroxycoumarin (10.0 g, 62 mmol) in acetone (120 mL) was added anhydrous K2CO3(13.8 g, 100 mmol) and triethylamine (2 mL) at room temperature. After stirring at room temperature for 30 min, 1, 2-dibromoethane (23.29 g, 124 mmol) was added to the reaction mixture, and whole was refluxed at 60°Cfor 24 h. The precipitate was filtered off and washed with acetone (4×100 mL).The solvent was evaporated under reduced pressure, and the residue was treated with water (100 mL) and extracted with dichloromethane (4×200 mL).The organic layer were combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure.The crude product was purified via silica gel column chromatography with mixed petroleum ether and ethyl acetate (5:1, v/v) as eluent, and resulted in a white solid.Compound 1.Yield55.18%.1H NMR (500 MHz, CDCl3) δ 7.65-7.64 (d, 1H, H-4,J= 9.5 Hz), 7.41-7.39 (d, 1H, H-5,J= 8.6 Hz), 6.89-6.86 (dd, 1H, H-8,J= 8.6, 2.4 Hz), 6.82-6.81 (d, 1H, H-6,J= 2.4 Hz) 6.28-6.27 (d, 1H, H-3,J= 9.5 Hz), 4.37- 4.34 (t, 2H, H-1’), 3.69-3.66 (t, 2H, H-2’).13C NMR (126 MHz, CDCl3) δ 161.32, 161.13, 155.91, 143.40, 129.09, 113.71, 113.21, 112.97, 101.84, 68.34, 28.54. ESI-MS m/z: 269.15 ([M]+). |
| 55.18% |
Stage #1: 7-hydroxy-2H-chromen-2-one With potassium carbonate; triethylamine In acetone at 20℃; for 0.5h;
Stage #2: ethylene dibromide In acetone at 60℃; for 24h; |
15.1. Procedure for synthesis of intermediate coumarin bromides A1-A5
General procedure: The intermediate coumarin bromides A1-A5 were synthesized as reported in a previous study. The synthetic route is illustrated in Scheme 1. For example, anhydrous K2CO3 (13.8 g, 100 mmol) and triethylamine (2 mL) at room temperature were added to a solution of 7-hydroxycoumarin (10.0 g, 62 mmol) in acetone (120 mL). After stirring at room temperature for 30 min, 1, 2-dibromoethane (23.3 g, 124 mmol) was added to the reaction mixture, which was then refluxed at 60°C for 24 h. The precipitate was filtered and washed with acetone (4 × 100 mL). The solvent was evaporated under reduced pressure, and the residue was treated with water (200 mL) and extracted with dichloromethane (4 × 250 mL). The organic layer was combined, dried with anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified via silica gel column chromatography with a mixture of petroleum ether and ethyl acetate (5:1, v/v) as the eluent, yielding in a white solid. |
| 50% |
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 96h; |
|
| 42% |
With potassium carbonate In acetonitrile for 2h; Reflux; |
4.2.2. General procedure for the synthesis of 3a-h
General procedure: K2CO3(12mmol) and dibromide derivatives (6mmol) were added to a solution of 1a(2mmol) in CH3CN (20mL). The reaction mixture was refluxed for 2h. Upon completion, K2CO3 was removed by filtration and the solvent was concentrated under vacuum, the residue was dissolved in CH2Cl2, washed with water, brine, dried over anhydrous Na2SO4and concentrated under vacuum to give compounds 3a-h and purification coloumn chromatograph (Eluent; Hexane-EtOAc; 4:1) [38]. 7-(2-bromoethoxy)-2H-chromen-2-one (3a). White powder, 42% yield; IR: 3081, 1727, 1711, 1605, 1556, 1508, 1393, 1353, 1268, 1226, 1202, 1122, 1096, 1010, 990, 891, 831, 806, 760, 615, 572, 546, 483, 461cm-1; 1H NMR (DMSO-d6, 300MHz) δ/ppm: 3.84 (2H, s, br), 4.40 (2H, s, br), 6.31 (1H, dd, J=2.6Hz, 9.3Hz), 6.97-7.04 (2H, m), 7.64 (1H, d, J=8.4Hz), 8.0 (1H, dd, J=2.0Hz, 9.6Hz); 13C NMR (DMSO-d6, 75MHz) δ/ppm: 31.7, 69.0, 102.1, 112.9, 113.4, 130.3, 144.9, 156.0, 160.9, 161.6, 162.6. |
| 39.7% |
With potassium carbonate In acetonitrile Reflux; |
1 4.1.5 General procedure for the synthesis of compound 9a-9c
General procedure: A mixture of coumarin derivative (1 eq), dibromoalkane (3 eq) and K2CO3 (6 eq) in 50mL acetonitrile was refluxed overnight. After the completion of reaction, excess K2CO3 was removed by filtration of celite and the filtrate was concentrated, washed with DCM and dried with Na2SO4. The residue was purified by column chromatography (EA: DCM: HEX=1:25:25) to afford the white solid. 4.1.5.1 87 7-(2-bromoethoxy)-2H-chromen-2-one (9a) (0029) Yield: 39.7%. 1H NMR (400MHz, DMSO-d6): δ 8.00 (1H, dd, J=9.5, 0.6Hz, C=CH), 7.64 (1H, d, J=8.6Hz, ArH), 7.03 (1H, d, J=2.4Hz, ArH), 6.98 (1H, dd, J=8.6, 2.5Hz, ArH), 6.30 (1H, d, J=9.5Hz, C=CH), 4.47-4.39 (2H, m, CH2), 3.88-3.79 (2H, m, CH2) ppm. 13C NMR (100MHz, DMSO-d6): 161.46, 160.67, 155.79, 144.71, 130.06, 113.25, 113.22, 113.19, 101.93, 68.85, 31.49ppm. |
|
With potassium carbonate In acetonitrile for 2h; Reflux; |
4.7 General procedure for the synthesis of compounds 11a-b
General procedure: K2CO3 (1.66 g, 12 mmol) and 1,2-dibromoethane (1.12 g, 6 mmol) were added to a solution of 10a or 10b (2 mmol) in CH3CN (20 mL). The reaction mixture was refluxed for 2 h. Upon completion, K2CO3 was removed by filtration and the solvent was concentrated under vacuum, the residue was dissolved in CH2Cl2, washed with water, brine, dried over anhydrous Na2SO4 and concentrated under vacuum to give compounds 11a-b, which were used in the next reaction without further purification. |
|
With potassium carbonate In acetone for 4h; Reflux; |
|
|
With potassium carbonate In acetone at 60℃; for 4h; |
|
|
With potassium carbonate In acetone at 60℃; Sealed tube; |
|
|
Stage #1: 7-hydroxy-2H-chromen-2-one With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 0.25h;
Stage #2: ethylene dibromide In N,N-dimethyl-formamide at 25℃; |
2.1.4. General procedure for the synthesis of 4-(2-bromoalkoxy)-2H-chromen-2-ones.
General procedure: 4-hydroxy coumarin (1 equiv) was dissolved in DMF and K2CO3 (1.5 equiv) was added to it. The mixture so obtained was allowed to stir for 15 mins. After 15 mins, dibromobutane (1 equiv) was added in the reaction mixture and was allowed to stir at room temperature until it was completed (monitored by analytical TLC). As the reaction completed, the reaction mixture was poured on crushed ice and set aside for a while (until the ice was completely converted into water), filtered and dried. The obtained crude product was purified using column chromatography using hexane: ethyl acetate (9.5: 0.5) to get pure 4-(4-bromobutoxy)-2H-chromen-2-one. |
|
With caesium carbonate; 4-methyl-2-pentanone at 110℃; |
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