Cinnoline oxidation

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). 

Oxygen 1 Sodium sulfide Cinnoline oxides s. 2, 340 NNftO NasS O... 

This method is exemplified by its application to quinoline, isoquinoline, cinnoline, and isoquinoline 2-oxide, which are nitrated as their conjugate acids. The rate profiles for these compounds and their N- or O-methyl perchlorates show closely parallel dependences upon acidity (fig. 2.4). Quaternisation had in each case only a small effect upon the rate, making the criterion a very reliable one. It has the additional advantage of being applicable at any temperature for which kinetic measurements can be made (table 8.1, sections B and D). 

Comparison of the behaviour of cinnoline 2-oxide (vi, i = O) with that of 2-methoxycinnolinium (vi, R = OMe) suggests that at high acidities the former is nitrated as its conjugate acid (vi, R = OH), but that as the acidity is lowered the free base becomes active. At high acidities 5- and 8-nitration are dominant, but as the acidity is lowered 6-nitration becomes increasingly important. The 5- and 8-nitro compounds are probably formed mainly or wholly by nitration of the conjugate acid, and the 6-nitro compound wholly or mainly from the free base. ... 

IV-Oxidation of cinnoline (2) with hydrogen peroxide in acetic acid results in the formation of four products cinnoline 1-oxide (92 26%), cinnoline 2-oxide (93 50%), cinnoline... 

When cinnoline 1-oxide is treated with nitric and sulfuric acids or potassium nitrate in sulfuric acid, 4-nitrocinnoline 1-oxide is obtained in yields ranging from 3-64% depending on the reaction conditions. With a mixture of fuming nitric and sulfuric acids, the corresponding 4-nitro-, 4,5-dinitro- and a small amount of the 5-nitro-cinnoline derivatives are obtained. 

Both 4-nitrocinnoline 1-oxide and the 5-nitro isomer give 4,5-dinitrocinnoline 1-oxide when treated with fuming nitric and sulfuric acids. Cinnoline 1-oxide also reacts with benzoyl chloride/silver nitrate to give 3-nitrocinnoline 1-oxide in 71% yield. 

Nitration of cinnoline 2-oxide takes a different course. With nitric and sulfuric acids or with potassium nitrate and sulfuric acid a mixture of 8-nitrocinnoline 2-oxide, 6-nitrocinno-line 2-oxide and 5-nitrocinnoline 2-oxide is obtained, while with benzoyl nitrate in chloroform only a low yield (1.5%) of the 5-nitro derivative is obtained. 

The reaction of cinnoline 2-oxide with phenylmagnesium bromide gives phenanthrene, trans- and cfs-stilbene, 2,3-diphenyl-l,2-dihydrocinnoline and 2-styrylazobenzene in yields of 1-15%. Analogous results are also obtained from 4-methylcinnoline 2-oxide. 

Since the pyridazine ring is generally more stable to oxidation than a benzene ring, oxidation of alkyl and aryl substituted cinnolines and phthalazines can be used for the preparation of pyridazinedicarboxylic acids. For example, oxidation of 4-phenylcinnoline with potassium permanganate yields 5-phenylpyridazine-3,4-dicarboxylic acid, while alkyl substituted phthalazines give pyridazine-4,5-dicarboxylic acids under essentially the same reaction conditions. 

The photodecomposition of benzotriazine A/ -oxides produced 3-substituted 2,1-benzisoxazoles (Scheme 183) (73JA2390). The photolysis of cinnoline 1-oxides produced 3-methyl-2,1-benzisoxazoles (Scheme 183) (74TL2643, 74T2645). 

Barrellene oxide flash thermolysis oxirenes in, 7, 125 Basic Violet 10 (C.I. 45170), 3, 879 Batrachotoxin, 4, 374 Baumgarten method cinnoline synthesis, 3, 44... 

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 >. 

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,... 

Various pyridazine-A-oxides (including cinnoline A-oxides) have been prepared as potential antitumour agents in Japan [276-278]. Among several 4-nitro-pyridazine 1-oxides tested for activity against rat ascites hepatoma AH-13, 3,6-dimethoxy-4-nitropyridazine 1-oxide (74) has been found to be the most potent compound a minimal effective dose of 5 mg/kg has been estimated [276], Also pyridazine A-oxides of type (75) bearing a bis(2-chloroethyl)ami-nomethyl side-chain at C-6 have been reported to be effective (0.5-5 mg/kg, i.p.) against AH-13 in rats [278]. Both types of compound (74), (75, R = H, Br), however, have been shown to be inactive against mouse lymphoid leukaemia L-1210. 

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

Ring-opened products were obtained from pyrido[l,2-6]cinnolin-6-ium hydroxide inner salt (17, R = H) by oxidation with 3-chloroperoxybenzoic acid, or by reduction with Zn in acetic acid, and from the 5-methyl derivative 43 by reduction with Zn in acetic acid (74JHC125). 

Diazine A -oxides can be regioselectively formed with H2O2 in formic acid as exemplified by the reaction of 2-chlorobenzo[/]cinnolines, 2-chloro-5,6-dihydrobenzo[/]cinnolines, and 3-chloro-9//-indeno[2,l-f]pyridazines <2000AP341>. This area was extensively discussed in CHEC(1984) <1984CHEC(2)1>. 

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>. 

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