PHTHALIDE FORMATION

Abstract

3,5-Dimethoxy-6-chloromethyl-4-methylphthalide has been produced from 3,5-dimethoxy-p-toluic acid by heating with aqueous formaldehyde and hydrochloric acid. A chloromethylphthalide has been produced in a similar reaction from 5-methoxy-m-toluic acid, but its orientation has not been established. By treatment with potassium cyanide followed by hydrolysis this chloromethylphthalide has been changed to a phenylacetic acid. Oxidation with permanganate has opened the phthalide ring giving a tricarboxylic acid.When 5-methoxy-p-toluic, 5-methoxy-o-toluic, and 3,5-dimethoxy-o-toluic acids respectively are treated with formaldehyde solution and hydrochloric acid, the normal phthalides are produced. This conclusion has been verified by comparison with phthalides produced from the same acids by the Fritsch method. Hydrobromic or hydriodic acid may replace hydrochloric acid in these reactions. Attempts to employ aliphatic aldehydes other than formaldehyde in the reaction have been unsuccessful owing to polymerization of the aldehydes.