Isoindolenines reactions

An ingenious synthesis of 1-arylisoindolcs has been developed by Vebor and Lwowski, based upon the reaction of an o-phthalimido-methylbenzophenone (41, R = aryl) with hydrazine (Table IV). The benzophenone is prepared by a Friedel-Crafts reaction with o-phthalimidomethylbenzoyl chloride (40). The mechanism of isoindole formation can be represented sehematically by a sequence involving attack by hydrazine at the imide to give the ring-opened hj drazide (42), followed by cyclization to phthalazine-l,4-dione (44) with displacement of the o-aminomethylbenzophenone (43). Intramolecular condensation of the latter can lead, via the isoindolenine... 

Tetramethylisoindolenine (50) is obtained as an unstable, crystalline solid from the reaction of 2,5-hexanedione with 2,5-dimethylpyrrole in the presence of sulfuric acid. Treatment of the same diketone with ammonium sulfate also affords this isoindolenine. NMR measurements in deuteriochloroform indicate that a small amount of 1,3,4,7-tetramethylisoindole (51) is present in equilibrium with the isoindolenine. This same isoindole was postulated as an intermediate in the reductive self-condensation of 2,5-dimethyl-pyrrole (52) which affords a mixture of cis- and lwMs-l,3,4,7-tetra-methylisoindolines (53 and 54). Hydrolytic opening of the... 

Addition of DMAD to the carbonyl-stabilized nitrogen ylid 329 gave the furan 330 and the isoindolenine 331. This and similar reactions201 could involve either a symmetry allowed concerted cycloaddition or a nonconcerted reaction followed by elimination of the tertiary amine. 

Vollmann found that the reaction between Timino-3-amino isoindolenine (124) and 2-amino-4-methylthiazole is catalyzed by ammonium chloride and involves the exocyclic nitrogen (285). This reaction (Scheme 82) was later used to prepare dyes (286). 

Various routes to 1,1,3-trisubstituted 1//-isoindoles have been reviewed.5 Thus, the triphenyl derivative 53 is available from the reaction of benzo-phenone imine with diphenyldichloromethane or by the Friedel-Crafts reactions between benzene and l,l,3-trichloro-lf/-isoindole. Recently, another route, which involves heating the cyclotriphosphatriazene 54 with benzophenone, has been described.86 The nitrone derivative 55 of the isoindolenine 53 may be obtained by treating the isoindolenine with m-chloroperbenzoic acid. This nitrone has also been obtained by the isomerization of the oxaziran 56 in the presence of a Lewis acid (Scheme 11).87... 

The kinetic instability of isoindoles dominates the chemistry of the simple systems and is principally to be ascribed to autoxidation and self-condensation reactions. The self-condensation reactions appear to be more important when both isoindole and isoindolenine tautomers can coexist (Eq. 6) hence, in general, /V-substituted isoindoles are more stable than /V-unsubstituted compounds. Although the autoxidation reactions have been worked out in several cases (Section V,G), the self-condensations are less well understood (but see Section V,F). Isoindole and C-alkylisoindoles become dark when kept at room temperature.6,78 C-Arylisoindoles are somewhat easier to handle, but 2-amino-1,3-diphenylisoindole decomposes rapidly on exposure to light and air.60 Operationally, unless strongly electron-withdrawing substituents are present at carbon, isoindoles must be kept in the freezer under nitrogen. 

Figure 13.14 shows another route which in principle can lead to the formation of an unsymmetrically substituted phthalocyanine, in this case a monosubsti-tuted one. In this route the subphthalocyanine 1 is reacted with a monosubstituted isoindolenine 2 with formation of the monosubstituted phthalocyanine 3 [41-43,92]. This route has been applied for the preparation of a variety of unsymmetrically substituted phthalocyanines [41-43]. However, there are problems due to the arduous purification process lowering the yield. The crude reaction mixture includes, besides the desired subphthalocyanine, several side products due to polymerization and ring halogenation, which are difficult to eliminate. Recently two modified methods for the preparation of subphthalocyanine 1 (B = C1) have been described, which give a better yield [93] and higher purity [94]. 

---