Hydroxycinnolines, reduction

A number of cinnolines have been obtained by alkali treatment of isatins. Thus, 214 gave 215,88-70 while isatin on treatment with base followed by hydrogen and palladium, diazotization, and reduction gave 3-hydroxycinnoline.62 4... 

The alkylation of 3- or 4-hydroxycinnolines has been shown to occur at the 2-position. Reduction of these cinnolinium salts with lithium aluminum hydride gave 2-alkyl-l,2,3,4-tetrahydrocinnolines which darkened rapidly on exposure to air but could be converted to stable derivatives.1370,6... 

The difference between the two ways of controlling the electrolytic reaction is illustrated in Fig. 4, which shows polarograms of the cathc -lyte recorded during the controlled potential reduction (at —0.65 volt vs. SCE) in hydrochloric acid of 4-hydroxycinnoline (7) to l,2,3,4-tetrahydro-4-cinnolone (8).44... 

Fig. 4. Polarograms obtained during a controlled potential ( — 0.65 volt vs. SCE) reduction of 4-hydroxycinnoline. (a) Initial solution, (b) partly reduced solution, and (c) nearly completely reduced solution (see text).

Reduction of pyridazin-4-ones seems not to have been reported, f. Derivatives of Cinnoline. 3-Hydroxycinnoline (222)44 is reduced in a two-electron wave from pH 0 to 11. In strongly acid solution the main product is 1-aminooxindole (223), which is also obtained on reduction with zinc and sulfuric acid.232 Reduction in an emulsion of an aqueous phosphate buffer (pH 6.5) and n-butanol produced a nearly quantitative yield of 3-keto-l,2,3,4-tetrahydrocinnoline (224) this compound was easily reoxidized to 3-hydroxycinnoline. 

Hydroxycinnoline (LXXVI) [101] in acid solution is reducible in two, two-electron steps. The product from the first two-electron reduction is 4-keto-l,2,3,4-tetrahydrocinno-line (LXXVII). This compound is a derivative of phenylhydrazine and can thus be oxidized anodically in alkaline solution to an azo compound (LXXVIIT), which then tautomerizes to LXXVI. The carbonyl group of LXXVII is activated by the phenyl ring and—in contrast to 3-keto-l,2,3,4-tetrahydrocinnoline—is thus further reducible the reduction yields 4-hydroxy-1,2,3,4-tetrahydrocinnoline (LXXIX). On standing, this compound loses water with the formation of 1,4-dihydrocinnoline. If, however, the compound is oxidized in alkaline solution, the product (LXXX) loses water and forms cinnoline. 

Note. These reactions of acylcinnolines have been covered already reduction to alkylcinnolines (Section 2.2.1), some cyclocondensations (Section 4.1.2.2), and reduction to extranuclear hydroxycinnolines (Section 4.2). Their oxidation to cinnolinecarboxylic acids appears to be unrepresented in the more recent literature. Some other reactions are illustrated in the examples that follow. 

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