399. The preparation of some substituted homophthalic acids

Abstract

Addition of hydrogen cyanide to 3-phenacylphthalides in 2-methoxyethanol, followed by a two-stage hydrolysis, is a general method for the preparation of substituted homophthalic acids. gave a-(2-carboxy-3 : 4-dimethoxyphenyl)-p-(3 : 4-di-methoxybenzoy1)propionitrile (11; R = R' = R" = .R'" = OMe), which was converted by heat or mineral acids into the lactone of 3-(2-carboxy-3 : 4-dimethoxyphenyl)-5-(3 : 4dimethoxyphenyl)-2-hydroxypyrrole (111; R = R' = R" = R"' = OMe). This was then hydrolysed by alkali to a-(2-carboxy-3 : 4-dimethoxyphenyl)-P-( 3 : 4-dimethoxybenzoy1)propionic acid (IV; R = R' = R" = R"' = OMe) (Bailey and Robinson, J., 1950, 1375). This series of reactions has now been shown to be general for phenacylphthalides, the following phthalides having been taken through the sequence (I --+ IV) : 6 : 7-dimethoxy-3-4'-methoxyphenacylphthalide (I ; R = H, R' = R" = R"' = OMe), 6 : 7-dimethoxy-3fi-tolylphthalide (I; R = H, R' = Me, R" = R"' = OMe), and phenacylphthalide AUDITION of hydrogen cyanide to 6

Isocoumarins. Developments Since 1950

“…Hydrochloric acid or heat is sufficient to cyclize homophthalonitriles such as LXXXVIII (where R = methoxy and methyl groups) to isocoumarins of type LXXXIX. sequence has been used as a route to the chelidoninesanguinarine alkaloids (11)(12)(13). The nitriles are readily available from phthalides XC through the addition of hydrogen cyanide.…”