The general procedure for the synthesis of 6,7-dimethoxy-2H-benzo[d][1,3]oxazine-2,4(1H)-diones from benzyl chloroformate and 2-amino-4,5-dimethoxybenzoic acid is as follows:
1. 2-Amino-4,5-dimethoxybenzoic acid (25 g, 0.13 mol) was dissolved in tetrahydrofuran (THF, 400 mL).
2. Benzyl chloroformate (54 mL, 0.38 mol) was added slowly with vigorous stirring.
3. The reaction mixture was refluxed overnight, followed by evaporation to dryness and further removal of residual solvent under vacuum.
4. Ether (425 mL) was added to the residue followed by phosphorus tribromide (PBr3, 11.88 mL, 0.13 mol).
5. The mixture was refluxed for 48 hours, after which the reaction mixture was filtered and the solid was washed with ether (3 × 150 mL).
6. The residue was redissolved in ether, stirred for 1 h and then filtered, washed and dried to give 27 g of a white powdery product, 6,7-dimethoxy-2H-benzo[d][1,3]oxazine-2,4(1H)-dione.
Yield: 96%.
1H NMR (DMSO-d6, 200 MHz): δ 3.82 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 6.66 (s, 1H, Ar), 7.27 (s, 1H, Ar), 11.58 (s, 1H, exchangeable NH).
