Isoindoles self-condensation reactions

The kinetic instability of isoindoles dominates the chemistry of the simple systems and is principally to be ascribed to autoxidation and self-condensation reactions. The self-condensation reactions appear to be more important when both isoindole and isoindolenine tautomers can coexist (Eq. 6) hence, in general, /V-substituted isoindoles are more stable than /V-unsubstituted compounds. Although the autoxidation reactions have been worked out in several cases (Section V,G), the self-condensations are less well understood (but see Section V,F). Isoindole and C-alkylisoindoles become dark when kept at room temperature.6,78 C-Arylisoindoles are somewhat easier to handle, but 2-amino-1,3-diphenylisoindole decomposes rapidly on exposure to light and air.60 Operationally, unless strongly electron-withdrawing substituents are present at carbon, isoindoles must be kept in the freezer under nitrogen. 

Tetramethylisoindolenine (50) is obtained as an unstable, crystalline solid from the reaction of 2,5-hexanedione with 2,5-dimethylpyrrole in the presence of sulfuric acid. Treatment of the same diketone with ammonium sulfate also affords this isoindolenine. NMR measurements in deuteriochloroform indicate that a small amount of 1,3,4,7-tetramethylisoindole (51) is present in equilibrium with the isoindolenine. This same isoindole was postulated as an intermediate in the reductive self-condensation of 2,5-dimethyl-pyrrole (52) which affords a mixture of cis- and lwMs-l,3,4,7-tetra-methylisoindolines (53 and 54). Hydrolytic opening of the... 

A new methodology has appeared where 1-acyldipyrromethane was converted into the Pd-chelate of tram-A2B2 porphyrin in a one-flask reaction, in which the 1-acyldipyrromethane in refluxing EtOH containing KOH and Pd(MeCN)2 exposed to air simply self-condensed <05JOC3500>. Treatment of 4,7-dihydro-4,7-ethano-27/-isoindole and pentafluorobenzaldehyde... 

The condensation of 2,5-disubstituted pyrroles or 1,2,5-trisubstituted pyrroles with 1,4-diones under acidic conditions generates the isoindole system. This is a convenient route (i.e., with 2,5-disubstituted pyrroles) to JV-unsubstituted (and therefore potentially tautomeric) compounds.5 76-78 Certain isoindoles can be obtained directly from the 1,4-dione and ammonia or primary amine under acidic conditions77 or by the self-condensation of 2,5-disubstituted pyrroles under acidic conditions78 (Scheme 8). The pyrrole self-condensation may be rationalized as shown in Eq. (13) the other reactions are mechanistically analogous. 

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