Reactions of 3-(1-Hydroxyalkyl)phthalides with Acids: Synthesis of (Z)-3-Alkylidenephthalides and 3-Alkyl-8-hydroxyisocoumarins

Raghao S. Mali; Kantipudi N. Babu

doi:10.1021/jo971622e

Reactions of 3-(1-Hydroxyalkyl)phthalides with Acids: Synthesis of (Z)-3-Alkylidenephthalides and 3-Alkyl-8-hydroxyisocoumarins

J Org Chem. 1998 Apr 17;63(8):2488-2492. doi: 10.1021/jo971622e.

Authors

Raghao S. Mali¹, Kantipudi N. Babu

Affiliation

¹ Department of Chemistry, Garware Research Centre, University of Pune, Pune 411 007, India.

PMID: 11672109
DOI: 10.1021/jo971622e

Abstract

A new acid-catalyzed method for the synthesis of (Z)-3-butylidenephthalides 5 and a novel and general route to 3-alkyl-8-hydroxy/methoxyisocoumarins 6-8 from phthalides 9 is described. The hydroxyphthalides 4 and 10 were obtained by condensation of the phthalide anion with butyraldehyde and acetaldehyde. Reaction of hydroxyphthalides 4 with a mixture of orthophosphoric acid and formic acid gave the (Z)-3-butylidenephthalides 5, while the hydroxyphthalides 4 and 10 on reaction with p-toluenesulfonic acid provided the 3-alkylisocoumarins 6-8. The present approaches permit variation of the 3-substituent in isocoumarin and the pattern of functionalization on the aromatic rings of both isocoumarins and alkylidenephthalides.