Isoindole tautomers

Addition of pyridine to a benzene solution of this derivative was found to convert it from 80% of tho isoindole tautomer to 100% isoindole. 

The effect of solvent variation is illustrated in Table V. The results suggest that, with respect to the value in neutral solvents, hydroxylic solvents tend to favor the isoindolenine form (hydrogen-bonded as in 69), while solvents which act as an electron source for hydrogen bonding tend to stabilize the isoindole tautomer (as in 70). 

The effect of substituents is profound. Isoindole itself appears to be essentially present as the isoindole tautomer. As Table VI shows, a 1-methyl substituent shifts the ratio remarkably far to the isoindolenine side however, the effect is not additive since the 1,3-dimethyl system has a smaller proportion of isoindole tautomer than the 1-methyl.16 Aryl substituents in the 1,3-positions reestablish the isoindole tautomer (Table VI), presumably because conjugation between the aromatic systems is energetically more... 

Electron-withdrawing substituents at C-l (C-3), conversely, favor the isoindole tautomer 74. For the 1-methoxycarbonyl and 1,3-dimethoxy-carbonyl derivatives, only the isoindole form is detected. The X-ray structure of l-formyl-3-phenylisoindole95 reveals the isoindole tautomer with a N—H bond length of 0.95 A. The NMR spectrum in d6-dimethyl sulfoxide shows a sharp signal at <59.96 (—CHO) and a broad signal at <513.74 (NH). The isoindolenine form is not detected.25... 

Indole is a heteroaromatic compound consisting of a fused benzene and pyrrole ring, specifically ben2o[ ]pyrrole. The systematic name, IJT-indole (1) distinguishes it from the less stable tautomer 3JT-indole [271-26-1] (2). Iff-Indole [120-72-9] is also more stable than the isomeric ben2o[ ] pyrrole, which is called isoindole, (2H, (3) and IH (4)). A third isomer ben2o[i ]pyrrole is a stable compound called indoli2idine [274-40-8] (5). 

According to a molecular orbital calculation of Veber and Lwowski, isoindole should be favored over its tautomer, isoindolenine, by about 8 kcal/mole. However, the calculated electronic distribution is markedly different in the two oases, particularly at position 1, and it is to be expected that the nature and pattern of substituents will play an important role in determining the position of tautomeric equilibrium between these two species. 

Treatment of dimethyl sulfoxide (DMSO) is reported to lead to 2-phenylisoindole (17) in yields up to 40%. An interesting possibility in this case is involvement of the isoindole valence tautomer (67) as an intermediate. P. A. Barrelt, R. P. LinsteacI, G. A. P. Tuey, and J. M. Robertson, J. Chem. Soc. p. 1809 (1939). 

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-... 

Benz[/]isoindole 10 exists, on the basis of spectroscopic examination, predominantly in the benzenoid tautomeric form 10b, although the formation of the Diels-Alder adduct with N-phenylmaleimide suggests the presence of a small amount of the o-quinoid tautomer 10a (78JOC4469). 

Although isoindole itself exists preferentially as such (73JCS(Pl)1432, 72TL4295, 77TL1095), in accord with predictions of MO calculations (77JA8248 and refs, therein), the low resonance energy of isoindoles often results in the isoindolenine tautomer being favored in substituted derivatives. 1H NMR spectroscopy has been especially useful in the study of this tautomeric... 

Attempts to synthesize a condensed pentazine derivative by reaction of 6-chloro-l,2,4,5-tetrazino[3,2-a]isoindole (409) with sodium azide led to the isolation of 3-methyl-6-(2-cyanophenyl)-l,2,4,5-tetrazine (412) rather than the azide (410) or its valence tautomer (411) which contains a pentazine structure (Scheme 23) (82UP22100). 

As expected, alkyl substitution also favors the isoindolenine, although accurate quantitative evaluation of proportions of tautomers is made difficult here by the instability of these derivatives.42 NMR measurements of 1,3,4,7-tetramethylisoindolenine indicate that this tautomer predominates over the corresponding isoindole by about 8 1.39... 

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