Quinoxalino cinnolines

A smdy of the halogenation of polyaza heterocycles is in progress. In the case of quinoxalino[2,3-c]cinnolines it has been found that using HCl or HBr in chloroform halogenation occurs at C-10, with protonation atiV-12, and subsequent oxidative aromatisation (Scheme 19) < 96JCS(P1)1699 >. 

Some new syntheses have been published since 1982. The cyclization of 2-acetamido-Ar-(2-nitro-benzylidene)anilines (77) with potassium cyanide in methanol leads to quinoxalino[2,3-c]cinnolines (79) via the nitriles (78) (Scheme 14) <80JCR(S)208,87JCS(Pl)50l, 87JCS(P1)507>. 

AMI calculations have been performed on pyrazino[2.3-c]pyridazine and its N-protonated species.2 Energy levels and charge densities were calculated by Hiickel MO calculations.3 MNDO calculations have also been performed on a benzo-annulated pyrazino[2,3-c]pyridazine (quinoxalino[2,3-c]cinnoline).69... 

Cyclization of /V- [2-(2-nitrobenzylidene)amino]phenyl acetamides 3 with potassium cyanide in methanol leads to quinoxalino[2,3-c]cinnolines 5 which also contain the pyrazino[2,3-c]-pyridazine skeleton. The reaction is supposed to proceed via the addition of hydrogen cyanide to the N —C double bond (formation of 4) followed by formation of the quinoxaline ring and finally closing of the pyridazine ring. The yields obtained are up to 62%.78... 

Halogenation reactions are known for quinoxalino[2,3-c]cinnolines (3,4- and 6,7-bisbenzo-an-nulatcd pyrazino[2,3-c]pyridazines)69 and for pyridazino[3,4-6]quinoxalines (6,7-benzo-annu-lated pyrazino[2,3-c]pyridazines).77... 

Thus, a new route for the Beirut reaction is revealed in which a number of novel 2-amino-3-(2-nitrophenyl)quinoxalines, in addition to their expected 1,4-dioxides, can be easily prepared and converted into novel quinoxalino[2,3-c]cinnoline 5-N-oxide which are rare in literature. In these investigations the curious fact is the fortuitous finding that the methyl substituents of some of quinoxalino[2,3-c]cin-nolines, or their presumed 5-Af-oxides intermediates, can be easily converted into acetals or orthoesters which we believe to be unprecedented. 

Heterocycles 12 323-327. doi 10.3987/R-1979-03-0323 Haddadin MJ, El-Khatib M, Shoker TA, Beavers CM, Olmstead MM, Fettigner JC, Farba- KM, Kurth MJ (2011) Quinoxalino[2,3-c]cinnolines and their 5-A-oxide alkoxylation of methyl-substituted quinoxalino[2,3-c]cinnolines to acetals and oithoesters. J Org Chem 76 (20) 8421-8427. doi 10.1021/jo201687x... 

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