Benzo cinnoline 5-oxide

Amino-2 -nitrobiphenyls, which may be intermediates in some of the reductions, cyclize to benzo[c]cinnoline oxides on treatment with bases. This reaction provides a route to certain substituted monoxides of known orientation [Eq. (3)]. ... 

The benzo[c]cinnoline ring system is resistant to oxidation by chromic acid, but is oxidized to pyridazinetetracarboxylic acid by alkaline permanganate. " Benzo[c]cinnoline has been oxidized to the 5-oxide with hydrogen peroxide in acetic acid at 0°C, and further to the 5,6-dioxide at 110°-120 C. The JV-oxidation of various other derivatives has been reported, although the main method for the preparation of N-oxides has been by the reduction of 2,2 -dinitrobiphenyls (Section II,A,2). In the case of unsymmetrically substituted compounds, both of the above methods usually give mixtures of 5- and 6-oxides. Selectivity is occasionally observed, thus 4-bromobenzo[c]cinnoline is oxidized to the 6-oxide, presumably owing to steric factors. Benzo[c]cinnoline oxides of known orientation have been obtained by the cyclization of 2-amino-2 -nitro-biphenyl derivatives (Section II,A,2). 

Oxidative photocyclization of benzylideneaniline appears to proceed efficiently only in the presence of strong acid. The phenanthridine 31, however, has been prepared by irradiation of the imine 3228 few other examples of the photocyclization of arylimines have been reported.29 Strong acid is also required for successful photocyclization of azobenzenes to benzo-[c]cinnolines. Here, protonation is claimed to lower the reactive n, n excited state below the level of the unreactive n, it state. 2-Phenylazopyridine,... 

Dinitrobiphenyl, in an alkaline solution, is reduced to benzo[c]cinnoline N-oxide (Scheme 83) [122,123]. 

Microbial deoxygenation of benzo[f]cinnolin-5-ium oxide with Bakers yeast-NaOH in EtOH/water at reflux yielded 90% of benzo[f]cinnoline <1997TL845>. The same deoxygenation has been achieved in a similar yield via heating in EtOH with NaOEt at 160°C in a sealed tube <2004JOC7720>. 

Azobenzene is oxidatively cyclized to benzo(c)cinnoline (CIX) when exposed to sunlight in strongly acidic solutions,172 or in an acetic acid and ferric chloride mixture.124 As irradiation of azobenzene in neutral solutions is known to result in cis-trans equilibration, it seems that the... 

Only pyrazine and its benzo derivatives are easily converted into di-A-oxides, although di-A-oxides have been reported, for example, in the pyridazine, pyrimidine and cinnoline series. Oxidation of 3-amino-1,2,4-triazine 2-oxide with H202 in polyphosphoric acid at 24°C affords 3-amino-1,2,4-triazine 2,4-dioxide (78). However, 3-amino-1,2,4-triazine with peracetic or... 

Benzo[c]cinnoline derivatives of different oxidation levels are prepared by N-N bond formations from suitable 2,2 -disubstituted biphenyls as outlined in Scheme 5. 

Controlled reduction of 2,2 -dinitrobiphenyl is achieved with 2, 1, and 0.5 molar equivalents of sodium borohydride in the presence of palladium on carbon and sodium hydroxide to give benzo[c]cinnoline, its /V-oxide, and AT V -dioxide, respectively, in high yields (Scheme 6). 

By controlling the potential the reaction can be stopped at the N-oxide stage at more negative potentials the reduction can be controlled to give either benzo[c]cinnoline or its dihydro derivative. 

The oxidation of 5-aminophenanthridone with lead tetraacetate in methylene chloride leads to benzocoumarin and phenanthridone rather than benzo[c]cinnoline (cf. the oxidation of l-amino-3,4,5,6-tetraphenylpyridone349). 

Orientation in the nitration of the 5-oxide of benzo[c]cinnoline (11.20) depends upon conditions. With nitric acid alone it gives 69% of the 9-nitro 5-oxide and 13.5% of the 2-nitro 5,6-dioxide (62JCS2454). But with nitric acid/sulfuric acid, the products appear to be the 1- and 7-nitro 5-oxides in 43 and 26% yields, respectively. One group gives the yields as 43 and 26%, respectively (62JCS2454), whereas another finds the latter to be the major product (62JCS4384). 2,9-Dimethylbenzo[c]cinnoline 5-oxide and the 3,8-dimethyl isomer are nitrated at the 1- and 4-positions, respectively, as expected (62JCS4384). 

Benzo[c]cinnolines have been conveniently prepared by the cyclization of symmetrically disubstituted 2,2-diami-nobiphenyls using iodobenzene diacetate as the oxidant <1996J(P1)83, CHEC-III(8.01.9.1)72>. A similar oxidation of 2,2,6-triamino-6-propylthiobiphenyl 49 afforded a new tetracyclic ring system 50 (Scheme 25) <2000JOC6388>. 

Dinitrobiphenyl (57)44 88 is thus reducible in alkaline solution at a suitable potential to benzo[c]cinnoline N-oxide (58) in acid solution the reduction proceeds to 4,5-dihydrobenzo[c]cinnoline (59) which is very easily oxidized, e.g., by air, to benzo[c]cinnoline (60). 

At pH <1.5, however, A-oxides such as those of cinnoline,44 3,6-diphenylpyridazine,94 and pyrazine,254 give a two-electron polarographic wave followed by the reduction waves of the parent compounds. An attempt based on this to reduce a benzo-1,2,3-triazine-3-oxide to the parent compound failed as the compound was hydrolyzed too rapidly in strongly acid solution. 

Pyridazine was first synthesized by Tauber, who oxidized benzo[c]cinnoline to 3,4,5,6-pyridazinetetracarboxylic acid which was subsequently decarboxylated. All other syntheses of pyridazine, however, involve nuclear synthesis and are in the main cumbersome and characterized by poor yields. The reaction between a 1,4-ketoacid... 

The reduction of nitro compounds should initially produce nitroso compounds. This area has not been systematically explored because the nitroso group can be more easily introduced by alternative methods such as direct nitrosation, condensation and oxidative procedures. - In fact, there have been few instances in which nitroso compounds have been isolated as intermediates in reductions of nitro compounds. For example, it was initially believed that w-trifluoromethylnitrobenzene produced the corresponding nitroso compound upon reduction, but subsequently the product was shown to be w-trifluoromethylazox-ybenzene. - Low yields of an intramolecular dimeric, nitroso compound, benzo[c]cinnoline dioxide (1), can be obtained by reducing 2,2 -dinitrobiphenyl with zinc or sodium sulfide (equation I). - ... 

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]. 

The most widely used method for forming the benzo[c]cinnoline nucleus has been the reduction of 2,2 -dinitrobiphenyl (3) and its derivatives under alkaline conditions, analogous to the bimolecular reduction of nitroarenes. As in the latter reaction, the end product is a hydrazo compound (Scheme 1), in this case the cyclic 5,6-dihydrobenzo[c]cinnoline (6), but this is so easily oxidized back to the fully aromatic 1 that it is not isolated unless special precautions are taken (Section IV,D). Tauber originally employed 3% sodium amalgam in methanol or zinc and alkali to reduce 2,2 -dinitro-biphenyl, and these reagents have been used subsequently by other work-ers. ° Reductions using sodium sulfide or hydrosulfide and catalyst/hydrogen or catalyst/hydrazine systems have been used... 

However, another study by Emerson and Rees found that benzo[c]-cinnoline (1) was reduced more easily than the oxides 4 and 5 thus all three are probably reduced directly to the dihydro compound 6 under these conditions. They also concluded that 2,2 -dinitrobiphenyl (3), the most easily reduced of all, is converted into 2,2 -bis(hydroxylamino)biphenyl (7) in an eight-electron step and thence into 6 [Eq. (2)]. More recent studies by cyclic voltammetry indicate that some steps may be more complex. " It has also... 

Oxidations of 2,2 -diaminobiphenyls with sodium perborate, phenyl iodosodiacetate, ° or manganese dioxide have given benzo[c]cinnolines with hydrogen peroxide in acetic acid, cyclization is accompanied by N-oxidation. These reactions, which parallel the oxidation of arylamines... 

Benzo[c]cinnoline 5-oxide is formed when 2-azido-2 -nitrosobiphenyl is heated in toluene, possibly by cyelization to the dipolar intermediate (12), followed by elimination of nitrogen [Eq. (6)], or via 2-nitrosobiphenyl-2 -nitrene. The quantitative eonversion of 2,2 -diazidobiphenyl into benzo-[c] cinnoline by low-temperature photolysis was argued to provide evidence for a stepwise process through the azidonitrene and the dinitrene [Eq. (7)]. ... 

An early German patent first described the cyclodehydrogenation of azobenzene, 3,3 -dimethylazobenzene, and what was presumably 3,3 -dimethyl-4,4 -diaminoazobenzene to benzo[c] cinnolines by heating in melts of aluminum, potassium, and sodium chlorides in the presence or in the absence of air or oxidizing agents. The cyclization must proceed through... 

The ultraviolet spectrum of benzo[c]cinnoline in -hexane shows four band systems centred at approximately 250, 300, 350, and 400 nm. The first three of these are n-n bands, corresponding to those in the spectrum of phenanthrene, while the long-wavelength band, of low intensity, is due to an n-7T transition. In hydroxylic solvents this last band moves to shorter wavelengths and becomes obscured. Substituent effects, and those due to protonation and to A-oxidation, have been discussed in a series of papers by Holt and co-workers. ... 

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