Pokholenko O. Reaction of pyrido[2,1-а]isoindole and 2,4-dimethylpyrimido[2,1-а]isoindole with maleimides and synthesis of novel derivatives of annelated isoindoles.

Molecules of pyrido[2,1-a]isoindole and pyrido[2,1-a]isoindolium were studied crystallographically. Pyrido[2,1-a]isoindole was shown to have integral 14pi-electrone aromatic system with noticeable localization of peripheral double bonds in pyridine and benzene rings. Reaction between pyrido[2,1-a]isoindole and maleimides was systematically studied and found to lead to [2'-(1-R-2,5-dioxopyrrolidinylidene) - 2'-(1-R-2,5-dioxopyrrolidine)methyl] phenyl pyridines (E-diastereomers) as products of new rearrangement in the conditions of thermodynamic control. PMR spectra of the adducts present complicated patterns, variated with temperature change, thus indicating the dynamic processes of convertion atropoisomers. Coalescence temperature measurement gave the free activation energy of the convertion between the atropoisomers in the range of 78-80 kJ/mol. Analysis of spectral characteristics of obtained adducts lead to formulation of spectral criteria for identification of similar structures, containing 2'-(1-R-2,5-dioxopyrrolidinylidene) - 2'-(1-R-2,5-dioxopyrrolidine)methyl fragment. New derivatives of pyrazolo[5,1-a]isoindole were obtained, 5-methyl-1,3,4,5-tetrahydro- 2H- isoindolo[2,1-b]indazole was found to react with p-tolylmaleinimide with rearrangement, similar to described for pyrido[2,1-a]isoindole. Reaction of 2,4-dimethylpyrimido[2,1-a]isoindole with maleimides in the conditions of thermodynamic control was found to lead to 4-amino-2-R-9-(1-R-2,5-dioxotetrahydro - 1H-3-pyrrolyl)-2,3-dihydro - 1H-benzo[f]isoindole-1,3- diones, where R comes from maleimide component. Pyrido[2,1-a]isoindole and 2,4-dimethylpyrimido[2,1-a]isoindole react with maleimides in similar way until the 7-azanorbornene intermediate is formed. The difference of the intermediates is either CH group or N atom in the 1 position of azino[2,1-a]isoindole fragment. This difference seems to be the trigger of the further reaction pathway because of negative mesomeric and inductive effect of such nitrogen.