| 72% |
Stage #1: 5-Bromo-2-hydroxyacetophenone; N,N-dimethyl-formamide at -10℃; for 0.5h;
Stage #2: With trichlorophosphate at -10 - 20℃; for 16h; |
2 4.3.2 Synthesis of 6-bromo-4-oxo-4H-chromene-3-carbaldehyde (15)
A solution of 5'-bromo-2'-hydroxyacetophenone (14) (6 mmol) and anhydrous N,N-dimethylformamide (12 mL) was stirred at a temperature of -10 °C for 30 min. Phosphoryl chloride (POCl3) (12 mmol) was added dropwise during 1 h. The mixture was stirred at room temperature for 15 h and poured into water (40 mL) [42]. The product was filtered and washed with ethyl ether (2 x10 mL). Yield: 72%. 1H NMR (400 MHz, DMSO-d6) δ: 10.10 (1H, s, COH), 8.96 (1H, s, H(2)), 8.20 (1H, d, J = 2.5 Hz, H(5)), 8.05 (1H, dd, J = 8.9, 2.5 Hz, H(7)), 7.76 (1H, d, J = 8.9 Hz, H(8)). 13C NMR (101 MHz, DMSO-d6) δ: 189.4 (COH), 175.1 (C4), 165.2 (C2), 156.0 (C8a), 139.1 (C7), 128.7 (C5), 127.6 (C4a), 122.9 (C6), 121.4 (C8), 120.6 (C3). |
| 53% |
With trichlorophosphate at 0 - 20℃; for 1.5h; |
|
| 24% |
With trichlorophosphate at 0 - 20℃; |
3 Synthesis of 6-substituted 4-oxo-4H-chromene-3-carbaldehydes
General procedure: POCl3 (112.6 g, 0.72 mol) was added slowly to a well stirred and cooled (0-5 °C) mixture of N,N-dimethylformamide (53.6 g, 0.72 mol), o-hydroxyacetophenone c1 (20.1 g, 0.14 mol) for 30 min. The ice bath was removed and the mixture was further stirred for 8-12 h at room temperature. The orange-yellow colored organic mass was poured into crushed ice (400 g) with stirring, extracted with EtOAc (8 * 50 mL) and the layers were separated. The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. Thus obtained residue was subjected to column chromatography purification on silica gel . |
|
With trichlorophosphate at 60℃; |
|
|
With trichlorophosphate at 20℃; for 12h; |
|
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Stage #1: 5-Bromo-2-hydroxyacetophenone; N,N-dimethyl-formamide With trichlorophosphate
Stage #2: With water |
|
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Stage #1: 5-Bromo-2-hydroxyacetophenone; N,N-dimethyl-formamide With trichlorophosphate
Stage #2: With water |
|
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With oxalyl dichloride at 0 - 20℃; |
General procedure for the synthesis of 4-oxo-4H-chromene-3-carbaldehydes using oxalyl chloride (4a-j):
Oxalyl chloride (4.7 g, 35 mmol) was added slowly to a well stirred and cooled (0-5 0C) mixture of N,N-Dimethylformamide (2.5 g, 35 mmol), 1-(2-hydroxyphenyl)ethanone (1 g, 7 mmol) for 30 min. The ice bath was removed and the mixture was further stirred for 8-12 h at room temperature. The orange-yellow colored organic mass was poured into crushed ice (20 g) with stirring, extracted with chloroform (2 x 30 mL) and the layers were separated. The organic layer was dried over sodium sulfate and the solvent was removed under reduced pressure. Thus obtained residue was subjected to column chromatography purification on silica gel to give 4-oxo-4H-chromene-3-carbaldehyde (4a) in 86% yield. The similar procedure was adopted in making other chromene carbaldehydes (4b-j). |
|
With trichlorophosphate at -5 - 0℃; |
|
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With trichlorophosphate at 20℃; |
|
|
With trichlorophosphate |
General Procedure for the preparation of 3-vinyl chromones 1a-e and 1l-v
General procedure: The substituted 4-oxo-4H-chromene-3-carbaldehydes were prepared by Vilsmeier-Haack synthesis of 2′-hydroxyacetophenones following literature produces. [3] |
|
With trichlorophosphate at 0 - 65℃; |
|
|
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.166667h; Inert atmosphere;
Stage #2: 5-Bromo-2-hydroxyacetophenone In chloroform at 20℃; for 16h; Inert atmosphere; Reflux; |
|
|
With trichlorophosphate at 0 - 64℃; for 4h; |
1. General procedure for the synthesis of compounds 1a-1t
General procedure: To a cooled (0°C)solution of 2'-hydroxyacetophenone (1 g, 1 eq) in DMF (30 mL) was added phosphorusoxychloride (5 eq). The mixture stirred at 64 °C for 4 h until the 2'-hydroxyacetophenone consumed completely (TLC). The reaction was quenched withglacial water (100 mL), and the mixture stirred for an additional 30 mins. Then themixture was extracted three times with dichloromethane (100 mL). And then the solventwas evaporated in vacuo and the crude product was purified by column chromatographyon silica gel. |
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With trichlorophosphate at 0℃; for 2h; |
|
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With trichlorophosphate at 20℃; |
|
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Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃;
Stage #2: 5-Bromo-2-hydroxyacetophenone at 20℃; |
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