Hydrochloric Acid → 6-Methoxyphthalide

Participants

Reaction Conditions

Reaction Steps

Formaldehyde 48% v/v (65 ml, 0.86 moles) under stirring, then 3-methoxy-benzoic acid (100 g, 0.66 moles) were added to concentrated HCl (1 l) and the mixture was heated at 100° C. by checking the development of gas for 30 minutes. The cooling of the mixture brought to the formation of a precipitate which was filtered and put aside, while the mixture was washed with water, then with 5% NaOH. The new precipitate was extracted twice with CH2Cl2, the extract was 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 with CH2Cl2. The organic phase was washed with 10% NaOH, decoloured 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 concentrated. The residue was dissolved in CH2Cl2 and treated with 10% NaOH under stirring for 30 minutes. The organic phase was washed with water, dried and concentrated to give a solid which was crystallised from aqueous CH3OH. The filtrate was dried at 50° C. on P2O5, then crystallised again from aqueous CH3OH to give 35.28 g of the title compound (yield: 32%).

Provenance & Evidence