Synthesis of 1,1,3,3-Tetraalkylisoindolines Using a Microwave-Assisted Grignard Reaction
Richard C. Foitzik A , Steven E. Bottle B , Jonathan M. White C D and Peter J. Scammells A EA Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville VIC 3052, Australia.
B School of Physical Sciences and Chemical Sciences, Queensland University of Technology, GPO Box 2434, Brisbane QLD 4001, Australia.
C School of Chemistry, University of Melbourne, VIC 3010, Australia.
D Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, VIC 3010, Australia.
E Corresponding author. Email: peter.scammells@vcp.monash.edu.au
Australian Journal of Chemistry 61(3) 168-171 https://doi.org/10.1071/CH08008
Submitted: 11 January 2008 Accepted: 16 February 2008 Published: 26 March 2008
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).
Acknowledgements
The authors thank the Australian Research Council Centre of Excellence for Free Radical Chemistry and Biotechnology for financial support, and Associate Professor David Young from Griffith University for assistance with the high-pressure reactions.
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