Tautomerism isoindole

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... 

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. 

Syntheses of phthalimidines (e.g., 30) do not in themselves constitute syntheses of isoindoles or isoindolenines, since the lactam from shows no tendency to tautomerize, as discerned from spectroscopic evidence, to lactim forms (31 and 32). However, phthalimidines are... 

The reaction between phthalimidine (30) and triethyloxonium fluoroborate is reported to give the fluoroborate salt of 1-ethoxyiso-indolenine, from which the free base (35) can be liberated.The iso-indolenine (35) apparentlj shows no detectable tautomerism with the isoindole form (see Section IV, A). 

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-... 

Accurate, quantitative spectroscopic data for the simple alkyl-substituted derivatives of isoindole are not available, cither because of their inherent instability or tendency to tautomerize to isoindole-nines. However, the presence of an isoindole in a tautomeric mixture can be readily discerned by means of ultraviolet spectroscopy. ... 

As was pointed out earlier (76AHCS1, p. 217), tautomeric equilibria for substituted isoindole-isoindolenine systems depend critically upon the substituents. Isoindole exists in the o-quinoid form 6. Computational results for the parent systems are given in Table III (99UP1). The results indicate that within the B3LYP functional only large basis sets provide reliable energy differences. 

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). 

A possible mechanism for the observed transformation includes the sequence outlined in Scheme 2.327 (i) propargyl (A) - allene (B) tautomerization, (ii) 8jt-cyclization (C), (iii) N-0 cleavage (diradical D), (iv) diradical recombination (cyclopropanone derivative E), and (v) one or two step cyclizations of the azadienyl cyclopropanone into azepinone F. The occurrence of cyclopropanones (type E), as intermediates, is supported by the formation, in some cases, of isoindoles (type I) (789) as minor products (Scheme 2.327) (139, 850, 851). 

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... 

The p-Ka values for the NH acid dissociation of pyrrole and its benzo derivatives are closely similar. Recent measurements conducted in DMSO set the values at 19.90, 20.95 and 23.05 for carbazole, indole and pyrrole, respectively (81JOC632), although pKa values as low as 17.5 for pyrrole and 16.97 for indole have been recorded (67T2855). No reliable values are available for the NH dissociation of isoindole, as such measurements are complicated by the tautomeric equilibrium between the 1H and 2H isomers. It is apparent that many of the reactions conducted under strongly alkaline conditions and described in other sections could well proceed on the heterocyclic anions. In this section the discussion is centred upon reactions in which the C or N anionic species of the heterocycles are specifically produced. 

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