Pyrido isoindole

Synthetic routes to the benzocyclazines are analogues of those which lead to the cyclazines themselves. Representatives of the benzoh ]cycl[3.2.2]azine (indolizi no [3,4,5- ] isoindole, 365) ring system result from cycloaddition of, for example, DMAD to pyrido[2,l-tf]isoindole-6-carbonitrile 370 <1986H(24)3071> (Scheme 100). An alternative synthesis, which starts from the cyclazine 371 and involves construction of the additional benzenoid ring by a double Horner-Wadsworth-Emmons type of reaction, apparently gives the tetracyclic product 365 in only very low yields (Scheme 101) <1988H(27)2251>. 

Heating of 4-oxo-4//-pyrido[2,l-a]phthalazine-l-carboxylic acids or their esters (91) in methanolic potassium hydroxide or sodium methoxide yielded either 6-imino-4-oxo-6//-pyrido[2,l-a]isoindole-l-carboxylic acid (92) or ring-opened products (93) [92EUP472166 94H(37)239],... 

A deviation from the simple mechanism in Scheme 52 was observed with 2-pyridyl(2-naphthyl)carbene (282), from which a benzocarbazole, a pyrido[2,l-a]isoindole, and a benzindenopyridine were obtained (Scheme 53).232... 

Treatment of N-2,4-dinitrophenylpyridinium chloride (778) with phenyl-hydrazine in acetic acid causes reductive cyclization to yield the pyrido[l,2-ajimidazole (779). 3-Aminocrotononitrile, MeC(NH2)=CHCN, condenses with quinoline 1-oxide and isoquinoline 2-oxide to form the tricyclic compounds (780) and (781), respectively." The imidazo[5,l-a]isoquinoline derivative (783) is obtained by the action of phenyl isothiocyanate on the sodium salt of the Reissert compound (782)." ° Triethyl phosphite reduces the o-nitrophenyldipyr-rolylmethane (784 R=N02) to the nitrene (784 R = N), which forms the pyrrolo[3,2-6]quinoline derivative (785) by an intramolecular insertion reac-tion." 3-Amino-177-isoindole (786) reacts with acetylacetone in the presence of perchloric acid to yield the pyrimidoisoindolium salt (787). ... 

C. Xie, Y. Zhang, P. Xu, Novel synthesis of pyrido[2,l-fl]isoindoles via a three-component assembly involving benzynes, Synlett 20 (2008) 3115-3120. 

X. Huang, T. Zhang, Multicomponent reactions of pyridines, a-bromo carbonyl compotmds and silylaryl triflates as aryne precursors a facile one-pot synthesis of pyrido[2,l-a]isoindoles. Tetrahedron Lett. 50 (2009) 208-211. 

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