Synthesis of 3,4-dihydro-1(2H)-isoquinolinones

Citation
Hdh. Showalter et al., Synthesis of 3,4-dihydro-1(2H)-isoquinolinones, J HETERO CH, 38(4), 2001, pp. 961-964
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Organic Chemistry/Polymer Science
Journal title
JOURNAL OF HETEROCYCLIC CHEMISTRY
ISSN journal
0022-152X → ACNP
Volume
38
Issue
4
Year of publication
2001
Pages
961 - 964
Database
ISI
SICI code
0022-152X(200107/08)38:4<961:SO3>2.0.ZU;2-3
Abstract
Approaches toward the preparative-scale synthesis of target 3,4-dihydro-1(2 H)-isoquinolinones 1-3 are presented. Compounds 1 and 2 were prepared via a Schmidt rearrangement on easily obtained indanone precursors, but in low o verall yield. A better method to make this class of compounds is exemplifie d by the large-scale synthesis of 2 via a Curtius rearrangement sequence. T hus, high-temperature thermal cyclization of an in situ formed styryl isocy anate from precursor 8 in the presence of tributylamine gave the correspond ing 1(2H)-isoquinolinone (9). Catalytic hydrogenation of 9 provided the des ired 3,4-dihydro-5-methyl-1(2H)-isoquinolinone (2) in 65 % overall yield. S imilar reduction of a commercially available 5-hydroxy-1(2H)-isoquinolinone precursor 10 followed by an O-alkylation/amination sequence gave target 3 in good overall yield. The route proceeding via the Curtius rearrangement i s recommended for large scale synthesis of other 3,4-dihydro-1(2H)-isoquino linones. Only when deactivating substituents or sensitive functionality wit hin the benzenoid ring render the high temperature ring closure of the inte rmediate isocyanate inefficient might a Schmidt rearrangement protocol be t he method of choice.