Cinnoline 2-oxide

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... 

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. 

Cinnoline 2-oxide (113) underwent deoxidative cine-amination with primary or secondary amines to afford, for example, 3-propylaminocinnoline (114, R = NHPr) (neat PrNH2, reflux, 25 h 53%) or 3-(pyrrolidin-l-yl)cinnoline [114, R = N(CH2)4] [HN(CH2)4, reflux, 60 h > 95%]. ... 

A typical example of the cme-amination is interaction of cinnoline-2-oxide with an excess of primary or secondary amines, producing 3-aminocinnolines in 26-98% yields (Scheme 47) [105]. The lowest yield corresponds to the most bulky isopropylamine. It is evident that the reaction proceeds via the intermediate adduct 71 followed by its aromatization with elimination of water. Interestingly, the reaction of cinnoline-2-oxide with propylamine or pyrrolidine, which takes place in the presence of AgPy2Mn04, also affords the corresponding 3-aminocinnolines as the only products in 60 and 95% yields, respectively. Thus, even under oxidative conditions the cine-substitution pathway prevails on the oxidative amination. At the same time, as it has been already mentioned in Sect. 3.2 (Scheme 29), pyrimido-pyridazine A(2)-oxide 46 is aminated in the presence of AgPy2Mn04 both with loss of the N-oxide function and with its retention. 

Another fragmentation reaction leads to the formation of diazoketones from 1,4-diphenylphthalazine 2-oxide. Benzo-l,2,3-triazine 3-oxide and cinnoline 2-oxide also undergo ring fragmentation. 

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