| 89% |
With potassium carbonate In acetone for 16h; Reflux; |
General procedure for allylation of 1a-c.
General procedure: To a solution of phenol derivative (1, 10 mmol) anhydrous K2CO3 (4.15 g, 30 mmol) in acetone (30 mL) was added allyl bromide (1.81 g, 15 mmol). The mixture was heated under reflux and stirring for 16-18 h. After cooling to room temperature, the precipitated solid was filtered and washed with acetone. The filtrate was concentrated under reduced pressure and purified by column chromatography on silica gel using EtOAc/hexane as eluent to afford the corresponding allylic ether 2.25,267-(Allyloxy)-4-methyl-2H-chromen-2-one (2a). Yield 89%; white solid; mp 100-102 oC (from EtOAc-Hexanes) (lit41 mp 100-101 oC); Rf 0.68 (20% EtOAc/hexanes); IR (KBr): vmax 3076, 3020, 2953, 1725, 1611, 1392, 1349, 1285, 1263, 1208, 1141, 1069, 994, 936, 857, 838, 810 cm-1; 1H NMR (400 MHz, CDCl3): δ 7.49 (d, J 8.8 Hz, 1H), 6.88 (dd, J 8.8, 2.4 Hz, 1H), 6.83 (d, J 2.4 Hz, 1H), 6.14 (s, 1H), 6.11-5.94 (m, 1H), 5.44 (dd, J 17.2, 1.0 Hz, 1H), 5.34 (dd, J 10.6, 0.6 Hz, 1H), 4.60 (d, J 5.2 Hz, 2H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 161.63 (C), 161.26 (C), 157.26 (C), 152.50 (C), 132.25 (CH), 125.54 (CH), 118.48 (CH2), 113.74 (C), 112.81 (CH), 112.06 (CH), 101.82 (CH), 69.26 (CH2), 18.63 (CH3); MS (ESI+) m/z (%) 217.0 (M+H+, 100). |
| 89% |
With potassium carbonate In acetone at 60℃; for 12h; |
|
| 87% |
With potassium carbonate; potassium iodide In acetone for 12h; Reflux; |
General procedure for synthesis of 6-alkoxy- and 7-alkoxy-4-methylcoumarins (3a - i,4a - i)
General procedure: To the suspension of 4-methyl-6- or 7-hydroxy-2H-chromen-2-ones (2a or 2b,0.02 mol), respectively, in dry appropriate solvent (Tables 1 and 2) was added anhydrous potassium carbonate (0.04 mol, 5.5 g). The mixture was heated under reflux for 10 minwith stirring. Appropriate alkyl bromide or alkyl iodide was added and reaction mixturecontinued to heat under reflux for appropriate time (Tables 1 and 2). Solvent wasremoved completely under reduced pressure. Water (20 mL) was added to residue inorder to dissolve inorganic salts. The precipitate was filtered, washed with water untilpH 7, crystallized from 96% ethanol to yield the title compounds 3a-i, and 4a-i.Synthesis of several typical compounds was described below. |
| 86% |
Stage #1: 7-hydroxy-4-methyl-chromen-2-one With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.25h;
Stage #2: allyl bromide In N,N-dimethyl-formamide at 20℃; |
Synthesis of 7-Allyloxy-4-methyl-chromen-2-one (4):
A mixture of 7-Hydroxy-4-methyl-chromen-2-one (10.0 g, 56.8 mmol, 1.0 eq.) and potassium carbonate (11.8 g, 85.2 mmol 1.5 eq.) in dimethylformamide (30 mL) was stirred at room temperature. After 15 min, allyl bromide (9.9 mL, 113.6 mmol, 2.0 eq.) was added dropwise at 0 °C followed by continuous stirring at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was poured into an ice-water with vigorous stirring, resulted in an off-white solid, which was filtered off (10.6 g, Yield = 86%). |
| 82% |
With potassium carbonate In acetone for 12h; Reflux; |
Allylation of Hydroxycoumarins; General Procedure
General procedure: A mixture of the appropriate hydroxycoumarin (10.0 mmol), allylbromide (15.0 mmol, 1.3 mL) and anhydrous K2CO3 (30.0 mmol,4.2 g) in anhydrous acetone (25 mL) was heated to reflux for 12 h.The mixture was then cooled, filtered and the filtrate was concentratedunder reduced pressure. The residue was diluted with H2O(20 mL) and then extracted with EtOAc (2 × 20 mL). The combinedextract was washed successively with sat. aq NaHCO3 (2 × 20 mL),H2O (2 × 20 mL) and brine (30 mL), then dried (Na2SO4), filteredand the filtrate was concentrated under reduced pressure to leave acrude product, which was purified by column chromatography oversilica gel using EtOAc-PE as eluent. |
| 81% |
With potassium carbonate In acetonitrile at 70℃; for 0.25h; Microwave irradiation; |
|
| 75.8% |
With potassium carbonate In acetone for 5h; Heating; |
|
| 65% |
Stage #1: 7-hydroxy-4-methyl-chromen-2-one With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h;
Stage #2: allyl bromide In N,N-dimethyl-formamide at 20℃; for 0.5h; |
|
|
With potassium carbonate; acetone |
|
|
With potassium carbonate In acetone Heating; |
|
|
With potassium carbonate In acetone |
|
|
With potassium carbonate In acetone Heating; |
|
|
With potassium carbonate In acetone for 5h; Heating; |
|
|
With potassium hydroxide In methanol; water |
1 EXAMPLE 1
EXAMPLE 1 Exactly 35.2 g of 7-hydroxy-4-methylcoumarin was dissolved in 300 ml of methanol containing 11.2 g of KOH and 1.0 g of KI. Allylbromide, 24.2 g, was added and the mixture was refluxed for 5 hrs. The reaction mixture was then mixed with water and extracted with diethyl ether and the ether extract was concentrated and 40.3 g (93%) of 7-allyloxy-4-methylcoumarin was recovered by recrystallization from methanol. |
|
With potassium carbonate In acetone for 2h; Reflux; |
|
|
With potassium carbonate In acetone for 5h; Inert atmosphere; Reflux; |
7-(Allyloxy)-4-methyl-2H-chromen-2-one (2)18
To a mixture of 4-methylumbelliferone (1; 1.76 g, 10 mmol) and K2CO3 (1.65 g, 12 mmol) in acetone (10 mL/1 g of substrate) was added allyl bromide (1.1 mL, 12 mmol) and the reaction mixture was heated under reflux for 5 h. After cooling down to r.t., the inorganic material was removed by filtration, and the filtrate concentrated in vacuo to afford the title compound in essentially quantitative yield; yield: 2.2 g (98%). 1H NMR (300 MHz, CDCl3): δ = 2.40 (3 H, s, CH3), 4.60 (2 H, d, J = 5, 2 Hz), 5.34 (1 H, dq, J = 11, 1 Hz), 5.44 (1 H, dq, J = 17, 1 Hz), 6.05 (1 H, ddt, J = 17, 11, 5 Hz), 6.13 (1 H, s), 6.82 (1 H, d, J = 3 Hz), 6.88 (1 H, dd, J = 9, 3 Hz), 7.50 (1 H, d, J = 9 Hz, ArH). 13C NMR (75 MHz, CDCl3): δ = 18.6 (CH3), 69.2, 101.7, 111.9, 112.7, 113.6, 118.4, 125.4, 132.1, 152.4, 155.1, 161.2, 161.5. MS (ES+): m/z = 184 [M + H]+. HRMS: m/z calcd for C13H12O3 [M]+: 184.0883; found: 184.0880. |
| 0.6 g |
With potassium carbonate In acetone at 50℃; for 24h; Inert atmosphere; |
|
| 60 % |
With sodium carbonate In acetone at 70℃; |
|
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