Benzoisobenzofuran. Mechanistic Aspects of Isobenzofuran Formation from Acetals and Ortho Esters

Article abstract of DOI:10.1021/jo00161a020

Benzoisobenzofuran (1) is generated as a reactive intermediate by using the acetal 8 (R = Me, Et) with carboxylic acid catalysts, as shown by the formation of Diels-Alder adducts when the reaction is carried out in the presence of dienophiles ranging in reactivity from maleic anhydride to norbornene. Results with 8 generally parallel those observed earlier with 1-alkoxy-1,3-dihydroisobenzofuran (2).In contrast to the lower homologue 1,1-dialkoxy-1,3-dihydroisobenzofuran (4), which like the acetals gives Diels-Alder reactions, the ortho ester 9 fails to yield cycloadducts.With acetal 2, various kinetic parameters were explored.The rate of loss of 2 is half-order in mesitoic acid catalyst and follows second-order behavior with N-phenylmaleimide (NPM); i.e., the rate is proportional to the concentrations of 2 and NPM.The reaction of 2 appears to be zero order in dienophile with the less reactive norbornene.An alternative product must be formed reversibly under these conditions, and an oligomeric structure is suggested for this material.In the absence of dienophile a similar rate is observed, leading eventually to the presumed polymer in an irreversible reaction.Deuterium incorporation in recovered 2 when treated for a short time with CH3OD and acid catalyst provides evidence for the rapid reversible formation of isobenzofuran under the usual reaction conditions.This was further substantiated by deuterium incorporation in the Diels-Alder adducts from a reaction of 2 with norbornene in the presence of CH3OD.Ortho ester 4 reacts with various acids to give phthalide and ring-opened diesters, and these pathways are shown to dominate the reactions of 9.The different behavior of 4 and 9 in attempted Diels- Alder reactions is shown to be due to a higher barrier for formation (or lower stability) of 1-alkoxybenzoisobenzofuran, rather than more facile ring opening of 9 relative to 4.