[Formations and reactions of aromatic furazan compounds].
A reaction from various kinds of nitroquinoline with hydroxylamine in potassium hydroxide alkalinity produced a novel product, furazanoquinoline, besides the known amino derivatives. The products obtained were furazano [3,4-f] quinoline (5) from 5-nitroquinoline (1) and 6-nitroquinoline (6), and furazano [3,4-h] quinoline (10) from 7-nitroquinoline (8) and 8-nitroquinoline (11). The reaction mechanism was believed to be as shown in Figs. 2 and 3. The photoreaction of benzofuroxan (19) in acetonitrile containing a little water, under a high pressure mercury lamp, produced 1H-azepine-2,7-dione (20), while under irradiation using a low pressure lamp, 6H-furazano [4,5-c] carbazole-3-oxide (21) and compound 20 were obtained. Then the photoproduct 20 produced photodimer 22 by irradiation in acetonitrile: water (9:1, v/v) using a high or low pressure mercury lamp, while photolysis with alkali proceeded as in the photoreaction of N-alkylimide to give 7-hydroxy-1H-azepine-2-one (23). When pyrido [2,3-c] furoxan (24) was irradiated in acetonitrile containing a little water with a low pressure mercury lamp, 3-nitro-2-pyridone (25) was obtained. When compound 24 was irradiated in the presence of morpholine with a low pressure mercury lamp in an argon atmosphere, 6-morpholinopyridine 2,3-dioxime (26) was produced. Quinoxaline 1,4-dioxide derivatives (31, 33), phenazine 5,10-dioxide derivatives (36, 37) and pyrido [2,3-b] pyrazine derivatives (38, 39) were synthesized from the corresponding furoxan catalyzed by silica gel or molecular sieves, and their antibacterial properties were evaluated. The results of antibacterial screening tests in vitro, revealed strong activity against Bacteroides fragilis.
Difference in superoxide toxicity between 4,7-dicyanobenzofurazan and paraquat.
The O2-. production by aerobically cultured Escherichia coli in the presence of benzofurazan (1), 4,7-dimethylbenzofurazan (2), 4,7-dibromobenzofurazan (3), 4-bromo-6-cyanobenzofurazan (4), and 4,7-dicyanobenzofurazan (5) was examined by using the cytochrome c reduction method in order to elucidate the mechanism of cytotoxicity of benzofurazans. Adding compound 5 to E. coli cell suspension caused cytochrome c reduction, which was completely inhibited by superoxide dismutase. The rate of cytochrome c reduction was in the order of 1 = 2 = 3 less than 4 less than 5, which correlates well with that of the reduction potentials of these benzofurazans. Adding glucose to the E. coli cell suspension-compound 5-cytochrome c system accelerated the rate of cytochrome c reduction. The formation of 4,7-dicyanobenzofurazan anion radical in the cell suspension-compound 5-glucose system in the absence of O2 was followed by ESR spectroscopy. The ESR signal of the anion radical disappeared when O2 was added. Compound 5 was shown to have an approximately 10-fold greater increasing effect on the flux of O2-. by E. coli than paraquat (PQ) by the cytochrome c reduction method. The results were confirmed by the electrochemical method with an oxygen electrode. However, compound 5 had a bacteriostatic, but not lethal, effect, while PQ had both effects. The effect of compound 5 and PQ on lethality of E. coli showed a dramatic difference when E. coli was exposed to these two compounds and washed prior to testing the effects of that exposure. This difference probably arose because compound 5 readily leaked from the cells during dilution and plating. Also, the reduced form of compound 5 exits from the cells more readily than the reduced form of PQ and then generates O2-. in the medium by autoxidation. This suggests the importance of the intracellular production of O2-., rather than the extracellular production of O2-., for lethal effect.
The reactions of benzofurazan 1-oxides with enamines
Novel quinoxaline 1,4-dioxides are readily obtained from the reactions of benzofurazan 1-oxide and its derivatives with enamines. A general discussion of the reaction is presented.