Generic synthesis of substituted flavones; Flavones

JUMEL ([email protected]),
A contribution from the Caddick Group Group, UCL

Chemicals Used
2-hydroxyacetophenone (ACROS, 0.5g, 3.67 mmoles, 0.44 mL), benzoyl chloride (ACROS, 0.513 g, 3.67.10-3 moles, 0.43 mL, 1 eq.), solution of lithium bis(trimethyl)silyl amide in THF (Aldrich, 1M, 14.68.10-3 moles, 14.68 mL,4 eq.), tetrahydrofuran distilled form sodium/acetophenone (10 mL).

Procedure
The lithium bis(trimethyl)silyl amide in THF is added to a stirred solution of 2-hydroxyactephonenone in THF (5 mL) at -78°C (dry ice/acetone), over 10 min. The reaction mixture is stirred for 1h at -78°C, the warmed to -10°C (acetone/ice bath) stirred for 2h. The reaction mixture is re-cooled down to -78°C and a solution of benzoyl chloride in dry THF is added over 5 min. Stirring is continued for 30 min. at -78°C then warmed to room temperature and stirred fro 3h. The mixture is then quenched in a mixture of ice/water (70 mL) and concentrated HCl (3.7 mL), extracted with chloroform (3 x 10 ml) and the combined organic phases dried over magnesium sulfate, filtered and concentrated. To the resulting solid is added glacial acetic acid (18.5 mL), concentrated sulphuric acid (0.01 mL) and heated at reflux for 1 h. The reaction is quenched in iced water (70 mL), filtered and washed with water (5 mL). The solid is dissolved in DCM (15 mL), dried over magnesium sulfate, filtered and concentrated to afford the product (0.509g, 63% yield), which is deemed to be at good purity without need of further purification.

Author's Comments
A variety of halo, alkyl and methoxy functionalised flavones can be synthesised under these condition; these are introduced through the use of substituted 2-hydroxyacetophenones and benzoyl chlorides and enable functionalisation on both aromatic rings. Yields vary from 58-76%.

Data
1H NMR (CDCl3, 300 MHz) dH 8.26-8.23 (dd, 1H, J = 6.5 and 1.5 Hz, CH-C-C=O), 7.98-7.92 (m, 2H, ArH), 7.72-7.68 (m, 1H, ArH), 7.60.7.52 (m, 5H, ArH), 6.87 (s, 1H, C-CH-C=O).

Lead Reference
M. Cushman; D. Nagarathnam; Tetrahedron Letters; 1990; 31; 45; 6947-6500.

Other References

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