Synthesis of <i>N</i> ‐Acylisoindolinones, Phthalide, and a Benzo[ <i>c</i> ]furan by an Intramolecular Cannizzaro Reaction
The formyl group of o ‐phthalaldehyde ( OPA ) is highly reactive and can accept nucleophilic attacks from various reagents including less nucleophilic amides. Reactions of OPA with amides in the presence of acetic anhydride proceeds efficiently to afford the corresponding N ‐acylated isoindolinones, in which the modification of the N ‐acyl group is facilitated by only altering the amide. In this reaction, one of the formyl groups in OPA is oxidized and the other is reduced, that is, the intramolecular Cannizzaro (self‐redox) reaction. Furthermore, phthalide can also be obtained when sodium acetate is used as a nucleophile. While N ‐methylacetamide does not undergo the reaction, the less hindered cyclic secondary amide, 2‐pyrrolidone, reacts with OPA to furnish 1‐benzoyloxy‐1,3‐dihydro‐3‐(2‐oxo‐1‐pyrrolidino)benzo[ c ]furan, and the subsequent conversion to benzo[ c ]furan is successfully achieved upon treatment with t ‐BuOK.
Authors
- Ryoji Matsushima (ORCID: https://orcid.org/0009-0001-2416-9295)
- Kazuto Umezu
- Akitaka Ito (ORCID: https://orcid.org/0000-0002-0893-5535)
- Nana Hatayama
- Nagatoshi Nishiwaki (ORCID: https://orcid.org/0000-0002-6052-8697)
Institutions
- Kochi University of Technology (JP)
- Ihara Chemical Industry (Japan) (JP)
- Kumiai Chemical Industry (Japan) (JP)
Publication Details
- Journal
- European Journal of Organic Chemistry
- Published
- 2026-02-05
- DOI
- https://doi.org/10.1002/ejoc.202500867
- Citations
- 1
- Primary Topic
- Synthesis and pharmacology of benzodiazepine derivatives
- Type
- article
- Field-Weighted Citation Impact
- 22.95