Dibenzo cinnolines

The annelation of benzo rings on pyridazines was covered in CHEC-II(1996) <1996CHEC-II(6)1>. Maes and Matyus reported new examples in their synthesis of the dibenzo[// ]phthalazin-l(27r)-one and dibenzo[//]cinnolin-3(27/)-one skeleton. Palladium-catalyzed intramolecular arylation of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2//)-one yielded 2-benzyldibenzo[/,4]phthalazin-l(2//)-one. The synthesis of this new tetracyclic pyridazinone from 2-benzyl-5-(2-aminophenyl) -phenylpyridazin-3(2//)-one via a Pschorr-type reaction was also investigated. Similarly, the con-stmction of 2-methyldibenzo[/, ]cinnolin-3(2//)-one from 2-methyl-5-(2-bromophenyl)-6-phenylpyridazin-3(27T)-one and 2-methyl-5-(2-aminophenyl)-6-phenyl-pyridazin-3(2//)-one was performed <2003T5919>. 

Dibenzo[f,. ]cinnolines 259 have been obtained from 2-naphthylanilines 258 via diazotization followed by intramolecular electrophilic aromatic substitution (Equation 65) <2003BMC1475>. 

Related complexes having N—N-bonded bridging groups were isolated from the reactions of iron carbonyls with rigid cw-azo compounds, such as benzo[c]cinnolines (XXXVII) (177), dibenzo-l,4,5-oxadiazepine, 2,3-diazabicyclo[2.2.1]-hept-2-ene, and 4,5,9,10-tetrazapyrene. The latter compound gave a tetranuclear complex [C,2H6N4(Fe(CO)3)4] presumed to... 

Dinitrobiphenyl [101-104] is thus in alkaline solution at a suitable potential, reducible to benzo[c]cinnoline-7V-oxide in acid solution the reduction proceeds to 4,5-dihydrobenzo[c]cinnoline, which is very easily (e.g., by air) oxidized to benzo[c]cinnoline. A similar ring closure during the reduction of 2,2, 6,6 -tetranitrobiphenyl yields A-oxides of 4,5,9,10-tetraazapyrene [105-107]. Reduction of 2,2 -dinitrodiphenylsulfide yields via 2,2 -(bishydroxylamino)diphenylsulfide in strongly acidic or in alkaline solution dibenzo[Z)/]-l,4,5-thiadiazepine and its iV-oxide [108] under slightly different conditions the formation of 3-hydroxyphenothiazine has been reported [109]. 

Two ring-contractions of dibenzo[c,/][l,2]diazepine derivatives to a benzo[c]cinnoline have been reported. Attempted nitration of3,8-dichloro-(llH)-dibenzo[c,/][l,2]diazepine (19) in sulfuric acid gave 3,8-dichloro-benzo[c]cinnoline (20), and the same compound was obtained when the corresponding diazepinone (21) was allowed to react with ethyl 4-(dietho-xyphosphinyl)crotonate. ... 

When 2,2 -dianiinobiphenyl is bis-diazotized at 0°C (see also Section II,A,2) and the solution is neutralized with ammonia at that temperature, dibenzo[rf,/][l,2,3]triazepine (22) precipitates as a yellow solid (Scheme 4). Although moderately stable, 22 rearranges quantitatively to benzo[c]-cinnoline-5-imide (23) on heating in benzene. The imide (23) is also the... 

Cinnoline 1 (benzo[c]pyridazine), phthalazine 2 (benzo[ /]pyridazin), quinazoline 3 (benzo[benzene-fused diazines. Of the dibenzo-annulated systems, only phenazine 5 (dibenzopyrazine) will be discussed. 

C20H2gBrNOg, cis-5,6,13,13a-Tetrahydro-3,9-dihydroxy-1,2,10-trimeth-oxy-8H-dibenzo[a,fIquinolizine hydrobromide monohydrate, 35B, 199 C21H12N2O3, 6-Methylbenzo[g]naphtho[1,2-c]-cinnoline-7,12,14-trione, 35B, 201... 

Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11 H-isoquino[4,3-c]cinnoline-12-ones (e.g. ARC-31 ) with varied functionality at the 2-position of their ethyl substituents exhibit potent topoisomerase I (TOPI) targeting and antitumor activity. Similar results have been observed with the structurally-related analogs, 5-ethyl dibenzo[c,h][1,6]naphthyridines (e.g. ARC-111). The trimethylammonium iodide salt of both ARC-31 and ARC-111 can be readily prepared. Direct displacement of the trimethylammonium group by hydroxide, hydroxylated alkylamines and substituted ethylenediamines did provide a facile route for the preparation of 2-hydroxyethyl, several 2-(polyhydroxyalkyl)amino, as well as 2-(aminoethyl)amine derivatives. The relative TOPI-targeting activity and cytotoxicity of derivatives of both ARC-31 and ARC-111 with varied polar substituents at the 2-position of each of their ethyl substituents were determined. 

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