Properties of the Isoindole System

Two independent molecular orbital calculations (HMO method) of delocalization energies for isoindole and isoindolenine tautomers agree that the isoindole form should possess the more resonance stabilization. The actual difference calculated for isoindole-isoindolenine is about 8 kcal/mole, but increases in favor of the isoindole with phenyl substitution at position 1 (Table VI).Since isoindole and isoindolenine tautomers have roughly comparable thermodynamic stabilities, the tautomeric proce.ss is readily obser- 

It is of interest that the reversible migration of hydrogen between positions 1 and 2 of thi.s sj stem corre.spond to a 1,5-sigmatropie shift, a proee.s.s predicted to be favorable on theoretical grounds [R. R. Woodward and R. Hoffmann, J. Am. Ghem. Soc. 87, 2511 (1965)] and known to occur with exceptional facility (R. B. Woodward in Aromaticity, Spec. Publ. No. 21, p. 217. The Chemical Society, London, 1967). 

The isoindole-isoindolenine equilibrium has been studied quantitatively only in the case of certain 1-arylisoindoles. Although two structurally different isoindolenines are possible, only that with the carbon-nitrogen double bond conjugated with both aromatic rings was observed. Investigation of the isoindole-isoindolenine ratios for three compounds by NMR and ultraviolet spectroscopy indicated a 

Substituent Isoindole (%) Equilibrium constant (kcal/mole) 

It is apparent from simple valence bond considerations as well as from calculations of rr-electron density, that isoindoles should be most susceptible to electrophilic attack at carbon 1. This preference is most clearly evident when the intermediate cations (85-87) from electrophilic attack (by A+) at positions 1, 4, and 5 are considered. The benzenoid resonance of 85 is the decisive factor in favoring this intermediate over its competitors. 

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Syntheses from Phthalimidines Syntheses from Ortho-Disubstituted Benzenes Condensation of 1,4-Diketones with Amines and Pyrroles Other Reactions and Rearrangements Leading to Isoindoles IV. Properties of the Isoindole System A. Tautomerism... 

It seems useful to compare the chemical properties of indolizines with those of pyrroles, indoles and isoindoles. There is however one important exception, namely that cycloadditions involve the entire 7r-system of indolizines. 

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