Synthesis of Isoindol-1-one Derivatives from (3Z)-3-Benzylidene-2-benzofuran-1(3H)-one and Their Fungicidal Activity

Abstract

The recyclization of 3-benzylidenephthalide during the reaction with monoethanol-, thioethanol-, allyl- and benzylamines into N-substituted derivatives of isoindol-1-one was studied. The dependence of the structure of the products on the reaction conditions and the nature of the amine component was revealed. 3-Hydroxy-3-benzyl-2-(2-hydroxyethyl)- and 3-hydroxy-3-benzyl-2-(2-mercaptoethyl)isoindolin-1-ones, 2-allyl-3-benzyl-3-hydroxy- and 2,3-dibenzyl-3-hydroxyisoindolin-1-ones were formed when boiling benzylidenephthalide and amine at 56–70°C. An increase in the reaction temperature leads to the splitting off of the 3-hydroxyl group and the formation of either only the cis- and trans-isomers of N-substituted 3-benzylidenephthalide or a mixture of them with an admixture of 3-hydroxy precursor depending on the nature of the amine component and the boiling duration. In contrast, cis-N-substituted 3-benzylidenephthalide was predominantly formed when the 3-hydroxy precursor was treated with trifluoroacetic acid at room temperature. During acylation of the 3-hydroxy-2-(2-hydroxyethyl) precursor with acetic or 3-chlorobenzoic acid halides, along with esterification at the primary hydroxyl, a water molecule was also eliminated to form a mixture of (Z)- and (E)-3-benzylidene-N-[2-(2-acetoxyethyl- or -N-[2-(3-chlorobenzoyloxy)ethyl]isondolin-1-ones with a significant predominance of the (Z)-isomer. During esterification of this precursor with 3-chlorobenzoic acid under similar conditions, the 3-hydroxyl group is retained. The resulting compounds were studied as fungicides against the microscopic fungi Bipolaris sorokiniana, Fusarium oxysporum, and Rhizoctonia solani. All the tested compounds exhibited fungicidal activity against Rhizoctonia solani.