Isoindole, structure

It has been suggested (Ref. 98, but contrast Ref. 99) that isoindole can be regarded as made up of pyrrole and butadiene 7t-systems which are contiguous but virtually noninteracting. This view does not appear to receive adequate support from calculation or experiment on the isoindole structures referred to above and is at variance with the results of cycloaddition reactions which for the ground state typically occur across the 1,3-positions and not across the 4,7-positions (Section V,E). 

As expected, electron-withdrawing substituents at carbon in the isoindole structure slow down the cycloaddition to typical dienophiles. Thus, 4,5,6,7-tetrabromoisoindole is reported not to form a maleic anhydride adduct,35 and 2-methyl-4,5,6,7-tetrafluoroisoindole has been observed to react more sluggishly with dienophiles than either isoindole or 2-ethoxycarbonyl-isoindole.17 On the other hand, 2-alkyl-1-alkoxyisoindoles give 1 2-adducts (e.g., 83) in which both cycloaddition and substitution reactions have occurred.49... 

The major internal comparisons to be made within this chapter are between (13) pyrrole (1), furan (2), thiophene (3), selenophene (4) and tellurophene (5) b) pyrrole (1) and indole (6) (c) indole (6), benzo[6 Jfuran (7) and benzo[6]thiophene (8) d) indole (6), isoindole (9) and indolizine (10) and (e) benzo[6] and benzo[c] fused systems. The names of relevant heterocyclic radicals are given with the structures of the parent heterocycle. 

Several calculations of the electronic structure of isoindoles have Ijeen published, and the distribution of charge density around the isoindole nucleus calculated by these methods is summarized in X able I. A common prediction of the calculations, which are based on tlie LCAO-MO method or the frontier electron concept, is the relatively high electron density to bo found at position 1, and the expectation, thei efore, i.s that electrophilic substitution on carbon... 

Benzodiazepinones also undergo rearrangement to isoindoles when treated with acetic anhydride and pyridine (Py). The diazepinone (81), for instance, gives l-phenyl-3-acetylisoindole (82) under these conditions. The structure of the product was established in this case by comparison with (82) prepared by acetylation of 1-phenyl-isoindole. The rearrangement may be formally represented by a... 

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... 

Isoindoles are reactive toward oxidizing agents, and precautions usually advocated in the preparation of these compounds to prevent their oxidation merit careful consideration. The end products of oxidation are most often colored, resinous materials of indeterminate structure. The oxidative reactions appear to be accelerated by light and occur much more rapidly in solution than in the solid state. In a separate but possibly related process, certain isoindoles undergo polymerization in the solid state to give resins which, according to... 

Alkoxyisoindoles bearing substituents at the carbocyclic ring exist exclusively in the benzenoid structure the o-quinoid form could not be detected spectroscopically (88CB243). 3-(Methylthio)isoindoles are far more reactive than the corresponding alkoxy-isoindoles. These compounds prefer the benzenoid strueture, too (88CB243). 

The isoindolobenzazepine 380 obtained readily from prechilenine (139), 13-hydroxyoxyberberine (134), or oxybisberberine (130) (223), was recently isolated and named as chilenine (225). On reduction with zinc in hydrochloric acid-acetic acid 380 gave chilenamine (458) along with the hydroxylated product 459 (Scheme 94). Reduction of 380 followed by methylation and elimination of methanol gave pictonamine (460). On treatment with sodium hydroxide in aqueous methanol, 380 was converted to the isoindole 461, exposure of which to trifluoroacetic acid promoted cyclization and decarboxylation to afford the isoindoloisoquinoline neuvanine (462) (226). Its structure was revised (227) from the one originally proposed 463 (228). 

The foregoing examples show that the nucleophilic attack to nitroarenes at the o>T/ o-position followed by cyclization is a general method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion derived from ethyl isocyanoacetate as the reactive anion for the preparation of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyrimidines depending on the structure of nitroarenes (Eqs. 9.56 and 9.57).89 The synthesis of pyrroles is discussed in detail in Chapter 10. 

Methylisoquinol-l-one behaves as an enamine with dichlorocarbene to produce the dichlorocyclopropane derivative (83%). The corresponding reaction with dibromocarbene produces a thermally labile compound, which is assumed to have an analogous structure. Rearrangement of the dichloro compound under basic conditions leads to the isoindole derivative (96%), whereas controlled thermolysis... 

Additional examples of these novel SET-promoted photorearrangement reactions were uncovered in our investigations with the 2-azadienes 78 and 82. These substances yield the corresponding A-vinylaziridines 93 and 94, respectively, upon DCA-sensitized irradiation (Structures 93-99). The study was extended to azadiene 73. The DCA-sensitized irradiation of 73 yields the aziridine 95 and the dihydroisoindole 96 [65]. However, under these conditions, 2-azadiene 97 affords, in addition to the expected aziridine 98, the dihydroisoquinoline 99. The formation of the isoindole 96 can be explain by a pathway in which a radical-cation centered on the C—double bond attacks the phenyl ring at C-3, as shown in Scheme 15. The formation of the dihydroisoquinoline 99 can be justified by... 

Dihydronaphthalen-1,4-iwmes from Isoindoles The naphthalen-l,4-imine derivatives 91-99 have been obtained by addition of acetylenedicarboxylic esters to the appropriate isoindoles. 3- ss Some such adducts react further with acetylenic esters (see Sections III, G and H), so that A -ethyl- and A-n-butylisoindole give 1 2 adducts with dimethyl aoetylenedicarboxylate instead. iV-Methylisoindole appears to be exceptional in giving an oily 2 1 adduct, for which structure (100) was suggested on analogy with the 2 1 adduct obtained from l,3-diphenylbenz[c]furan and acetylenedicarboxylic acid. ... 

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