Synthesis of 2-Acetylbenzonitriles and Their Reactivity in Tandem Reactions with Carbon and Hetero Nucleophiles: Easy Access to 3,3-Disubstituted Isoindolinones

Abstract

2-Acetylbenzonitriles have been conveniently synthesized by the oxidation of the respective 2-ethylbenzonitriles, combining in a one-pot procedure radical bromination and hydrolysis reactions. The obtained ketones reacted under very mild conditions with carbon and hetero nucleophiles to give a wide range of 3,3-disubstituted isoindolinones in yields of 80–99 % by a tandem process consisting of an addition step and a subsequent Dimroth-type rearrangement. Among the tested nucleophiles, the addition of water in the presence of a catalytic amount of KOH allowed a convenient access to an unprecedented variety of novel 3-hydroxy-3-methylisoindolinones