Synthesis of 1,1,3,3-tetraalkylisoindolines using a microwave-assisted grignard reaction

Abstract

1,1,3,3-Tetraalkylisoindolines are important intermediates in the preparation of stable nitroxides, such as 1,1,3,3-tetramethylisoindolin-2-oxyl, 1, and 1,1,3,3-tetraethylisoindolin-2-oxyl, 2. The limiting step in their preparation is the Grignard reaction between N-benzylphthalimide and the appropriate alkyl magnesium bromide, which typically proceeds in yields of ∼28?40%. A microwave-assisted variation of this reaction has been optimized to give improved yields and reduced reaction times (45?60% and 2 h, respectively). © CSIRO 2008.