Hydrochloric Acid → 6-Methoxyphthalide

Participants

Reaction Steps

Concentrated HCl (1l) was added with 40% w/v formaldehyde (65 ml, 0.86 mole) under vigorous stirring, then with 3-methoxybenzoic acid (100 g, 0.66 mole) and the mixture was heated to 100° C. controlling the generation of gas, for 30 minutes. The cooling of the mixture yielded a precipitate which was filtered and stored, while the mixture was washed with water, then with 5% NaOH. The new precipitate was twice extracted with CH2Cl2, the extract anhydrified, concentrated, joined to the previously filtered solid and both were dissolved in CH2Cl2 and treated with diethylamine (120 ml, 1.15 moles). After 24 hours it was extracted with 10% HCl and the phases were separated and extracted with CH2Cl2. The organic phase was washed with 10% NaOH, discoloured with charcoal, anhydrified and concentrated. The residue was dissolved in CH2Cl2 and treated, under stirring, with 10% HCl for 30 minutes. The organic phase was washed with water, anhydrified and dried. The residue was dissolved in CH2Cl2 and treated with 10% NaOH under stirring for 30 minutes. The organic phase was washed with water, anhydrified and concentrated to give a solid which was crystallised from CH3OH/H2O 65:35 and dried at 50° C. over P2O5, then crystallised again from CH3OH/H2O 6:4 to give 35.28 g of the title compound (yield: 32%). m.p.: 115-117° C.

Provenance & Evidence