Dihydrophenazines

Nitrogen Compound Autoxidation. CycHc processes based on the oxidation of hydrazobenzene and dihydrophenazine to give hydrogen peroxide and the corresponding azobenzene—phenazine were developed in the United States and Germany during World War II. However, these processes could not compete economically with the anthrahydroquinone autoxidation process. 

The more traditional methods of phenazine synthesis falling into the type A synthesis are altogether less satisfactory than the application of the Beirut reaction. Traditionally, Ris prepared phenazine in low yield by heating o-phenylenediamine and catechol in a sealed tube at 200 °C (1886CB2206) however, the method appears to be unsatisfactory at best and gives, in addition to phenazine, 5,10-dihydrophenazine in varying amounts (Scheme 53). Several variants of this procedure exist o-benzoquinone has been used in condensation with 0-phenylenediamine and yields as high as 35% have been reported, and 1,2,3,4-tetrahydrophenazine has been prepared by condensation of o-phenylenediamine with cyclohexane- 1,2-dione. 

No practical type B syntheses of quinoxalines are commonly in use, largely because of the fact that type A syntheses are more facile however, some phenazine syntheses of this type are known, particularly those described in the older chemical literature. Hillemann (38CB42) has effected dimerization of 0-bromoaniline by heating its solution in nitrobenzene with K2CO3 and copper powder. The reaction is believed to proceed through the intermediacy of 5,10-dihydrophenazine, but the latter has not been isolated (Scheme 68). 

The reaction of benzyl radicals with phenazine gives 5,10-dibenzyl-5,10-dihydrophenazine (39) and 1-benzylphenazine (40) in the approximate ratio of 1 3. " ... 

Synthetic method 11 3-(N-benzyl-N-methyl)amino-9-ethyl-10-ben-zoyl-9,10-dihydrophenazine (62) (procedure from EP Patent Application 671,393).21 9-Ethylphenazinium ethosulfate (58) (obtained from phena-... 

Twelve grams of the magenta dye 61 was dissolved in 250ml of methylene chloride and stirred gently with a solution of 12.2g of sodium dithionite in 250 ml of water. A solution of 5 g of benzoyl chloride in 10 ml of dichloromethane was added slowly to the lower organic layer. The pH of the upper aqueous layer was maintained at 5 to 6. The organic layer was separated, washed with dilute aqueous NaOH and brine. The solution was absorbed onto silica gel and rotary evaporated to dryness. The product was washed from the silica with ether. The ether solution was evaporated to yield 8.2 g of the leuco dye 3-(A-benzyl-A-methyl)amino-9-ethyl-l0-ben-zoyl-9,10-dihydrophenazine (62). 

As observed, aromatic hydrocarbons gave products of protonation on dissolution in hydrofluoric acid. Oxidation into aromatic cation-radicals did not take place (Kon and Blois 1958). Trifluoro-acetic acid is able to transform aromatics into cation-radicals. This acid is considered a middle-powered one-electron oxidant (Eberson and Radnor 1991). Its oxidative ability can be enhanced in the presence of lead tetraacetate. This mixture, however, should be used carefully to avoid oxidation deeper than the one-electron removal. Thus, oxidation of 1,2-phenylenediamine by the system Pb(OCOCH3)4 -I- CE3COOH -P CH2CI2 leads to the formation of either primary or secondary cation-radicals. The primary product is the cation radical of initial phenylenediamine, whereas the secondary product is the cation radical of dihydrophenazine (Omelka et al. 2001). Sulfuric acid is also used as an one-electron oxidant, especially for aromatic hydrocarbons. In this case, generation of cation radicals proceeds simultaneously with the hydrocarbon protonation and sulfonation (Weissmann et al. 1957). 

Phenazine (9,10-diazaanthracene) was partially reduced by lithium aluminum hydride to 9,10-dihydrophenazine (yield 90%) [476 and totally reduced by catalytic hydrogenation over 10% palladium on carbon in ethanol at 180° and 50 atm to tetradecahydrophenazine (80% yield) [491 Catalytic hydrogenation of 1,10-phenanthroline afforded 1,2,3,4-tetrahydro- and sym-octa-hydrophenanthroline [497]. 

The system dihydrophenazine-phenazine shows a combination of redox and proton dissociation equlibria in aqueous solution summarised in Scheme 6.8. Phe-... 

It should be noted that, as all carbon positions in pyrazine are identical, the locant 2- in a monosubstituted derivative is unnecessary. All possible reduced derivatives of pyrazine 1, and several of those of its benzo analogues quinoxaline 2 and phenazine 3, are known. There are four dihydropyrazines, the 1,2-, 2,3-, 1,4-, and 2,5-isomers, two tetrahydropyrazines, the 1,2,3,4- and 1,2,3,6-, and hexahydropyrazine or piperazine, the last of which is omitted in this chapter. The reduced quinoxalines are the 1,2- and 1,4-dihydro compounds and 1,2,3,4-tetrahydroquinoxaline. The only known reduced phenazine is 1,4-dihydrophenazine. Hydroxypyrazine 4 and hydroxyquinoxaline 6 have been shown to exist in the tautomeric amide form by spectral studies, and therefore they are formulated as 2(1//)-pyrazinone 5 and 2(l//)-quinoxalinone, respectively. In contrast, aminopyrazine and aminoquinoxaline exist as described in the amino rather than the imino forms (Figure 1). 

Oxidation of 5,10-dialkyl-5,10-dihydrophenazines with hydrobromic acid in DMSO gives 10-alkyl-2(10/7)-phena-zinone in 52-79% yields (Equation 17) <1999JHC1057>. Depending on the alkyl substituents on C-5 and C-10 carbons, the parent phenazine is generated as the by-product. 

Tetranitro, C24H 4N608, and Hexanitro, C24H12N8012, derivs of 9,10-Diphenyl-9 I0-dihydrophenazine were not found in the literature thru 1966... 

A major group of photochemical reduction reactions are oxidation-reduction processes. As typical examples, phenazine (CXXI) and alloxan (CXXIII) are reduced by ethanol to give dihydrophenazine (CXXIl)/ 2 and alloxantin (CXXIV).42 Isatin (CXXV) in the presence of ace-naphthene (CXXVI) is reduced to isatide (CXXVII).204 The photoreaction proceeds at the expense of the alcohol, or (CXXVI) acetaldehyde and acenaphthylene (CXXVIII), are formed as by-products respectively. The formation of CXXVII may be due to the interaction of CXXV with the intermediate oxindole (CXXIX). 

Newer investigations316-318 have substantiated those previously published (Part I). Reductions in aprotic media in the presence of alkylating agents produced 5,10-dialkyl-5,10-dihydrophenazines.319... 

The anodic oxidation of phenazine N,AT-dioxide at a platinum anode in benzonitrile led to the intermediate radical-cation, which dimerizes.320,321 5-Substituted 5,10-dihydrophenazines are oxidized in two successive one-electron steps or one two-electron step in aqueous acetone.322 The corresponding phenazinium salts were formed as the ultimate oxidation products. 

Reduction of benzofuroxan (206)342 in neutral and alkaline solution first gives o-benzoquinonedioxime (207), which, as other oximes, is reduced with cleavage of the N—O bond to the diimine (208). The diimine then undergoes a two-electron reduction to o-phenylenediamine (209) or condenses with 209 to 2,3-diamino-9,l0-dihydrophenazine 210 [Eq. (120)]. 

Phenazine in methanol, with DMAD, gives the dihydrophenazine 500, a reduction having taken place.351... 

The reductive silylation under these conditions renders possible an access to useful heterocyclic intermediates which undergo various electrophilic displacements (Scheme 21)105 of the TMS moiety. In the first step phenazine (149) is converted to the corresponding 5,10-bis(TMS)-5,10-dihydrophenazine (150) that can be acylated in excellent yields to the desired 5,10-diacetyl-5,10-dihydro-phenazine (151). 

Cyclization of nitroanilinocyclohexenones 66 gives 3,4-dihydrophenazin-l(2//)-ones 67 in generally good yields (Scheme 38) <1982S852>. 

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