Highly Regioselective One‐Pot Synthesis of 7‐Hydroxy‐6‐methylphthalide from 3‐Hydroxy‐4‐methylbenzylalcohol

Abstract

7‐Hydroxy‐6‐methylphthalide 2 was synthesized with high regioselectivity and moderate yield using a novel one‐pot synthesis that employed 3‐hydroxy‐4‐methylbenzylalcohol 1 and formaldehyde in the presence of tin(IV) chloride as catalyst and triethylamine as base. The proposed mechanism of the formation of 2 involves ortho‐formylation followed by hemiacetal formation and oxidation.

Keywords:

• 3‐Hydroxy‐4‐methylbenzylalcohol
• 7‐hydroxy‐6‐methylphthalide
• one‐pot synthesis
• regioselective

Acknowledgment

The author thanks the National Institutes of Health for its financial support (Grant No. GM54779).