REACTIONS OF 3-(1-HYDROXYALKYL)PHTHALIDES WITH ACIDS - SYNTHESIS OF (Z)-3-ALKYLIDENEPHTHALIDES AND 3-ALKYL-8-HYDROXYISOCOUMARINS

A new acid-catalyzed method for the synthesis of (Z)-3-butylidenephtha lides 5 and a novel and general route to 3-alkyl-8-hydroxy/methoxyisoc oumarins 6-8 from phthalides 9 is described. The hydroxyphthalides 4 a nd 10 were obtained by condensation of the phthalide anion with butyra ldehyde and acetaldehyde. Reaction of hydroxyphthalides 4 with a mixtu re of orthophosphoric acid and formic acid gave the (Z)-3-butylideneph thalides 5, while the hydroxyphthalides 4 and 10 on reaction with p-to luenesulfonic acid provided the 3-alkylisocoumarins 6-8. The present a pproaches permit variation of the 3-substituent in isocoumarin and the pattern of functionalization on the aromatic rings of both isocoumari ns and alkylidenephthalides.