Synthesis and Structural Study of New Saturated Isoindol-1-one Derivatives

Abstract

Condensation of 2-p-toluoy1cyclohexanecarboxylic acid (la,b) with primary amines gave the corresponding hexahydroisoindol-I-ones (2a-g) in good yield. The octahydro derivatives (4a-g) were prepared from cis- and trans-hexahydro- 1 (2H)-phthalazinone (3a,b)hy reductionwith zinc-hydrochloricacid viaring contrac- tion. Stereoselective synthesis of cis-N-phenyloctahydroisoindol-I-one (4h) was performed starting from 2b by reduction with magnesium-methanol at room temperature. Configurational assignments of cis and trans isomers were based on 'H- and L3C-nmr spectroscopic studies. The 3-arylisoindol-1-one derivatives have been associated with important pharmacological properties, such as antiarrhytmic, antitussive, and antiinflammatory activities among Synthesis of these compounds was carried out mostly from corresponding 1.4-dicarbonyl compounds by reductive cyclisation with primary amine~.~.~ Yamamoto eta/. prepared N-phenyl substituted isoindolines from aromatic isocyanates7 In the course of our work we investigated the reactions ofthe cyclohexane condensed keto acids with primary amines, with the aim to synthesize pharmacologically active derivatives. The conditions of these reactions were strongly determined by the basicity of applied amines. Alkyl- or cycloalkylamines (e.g cyclohexylamine) reacted readily under relatively mild conditions (reflux in benzene or toluene for several hours) with keto acid (la,b) but