Phenazine oxidation

The synthesis of phenazine derivatives and phenazine oxide based on the condensation of aromatic nitro compounds with aromatic amines in an alkaline medium (sodium hydroxide), reported for the first time by Wohl [12] in 1901, was of similar character ... 

Phenazine oxide reacts with Grignard reagents to give phenazinium salts. ... 

The mechanism of oxidative dyeing involves a complex system of consecutive, competing, and autocatalytic reactions in which the final color depends on the efficiency with which the various couplers compete with one another for the available diimine. In addition, hydrolysis, oxidation, or polymerization of diimine may take place. Therefore, the color of a mixture caimot readily be predicted and involves trial and error. Though oxidation dyes produce fast colors, some off-shade fading does occur, particularly the development of a red tinge by the slow transformation of the blue indamine dye to a red phenazine dye. 

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. 

Phenazine gives rise to an AA BB NMR spectrum with coupling constants /i,2 9,0, /i,3 1.67, /i,4 0 and Jx3 6.55 Hz (66CPB419). Similar coupling constants are also observed in a number of phenazines and phenazine iV-oxides. 

The ease of oxidation varies considerably with the nature and number of ring substituents thus, although simple alkyl derivatives of pyrazine, quinoxaline and phenazine are easily oxidized by peracetic acid generated in situ from hydrogen peroxide and acetic acid, some difficulties are encountered. With unsymmetrical substrates there is inevitably the selectivity problem. Thus, methylpyrazine on oxidation with peracetic acid yields mixtures of the 1-and 4-oxides (42) and (43) (59YZ1275). In favourable circumstances, such product mixtures may be separated by fractional crystallization. Simple alkyl derivatives of quinoxalines are... 

Cerium(IV) ammonium nitrate in methanol has been used to oxidize phenazine to the mono-N-oxide (41) in good yield (75JCS(P1)1398), but no other reports on the application of this reagent to the pyrazine or quinoxaline series have appeared. 

Phenazine mono-N-oxides have also been prepared from nitrobenzene derivatives. Condensation of nitrobenzene with aniline using dry NaOH at 120-130 °C results in modest yields of phenazine 5-oxide, although the precise mechanism of this reaction is not well understood (57HC(ll)l) with unsymmetrical substrates it is not possible to predict which of the isomeric fV-oxides will be produced. Nitrosobenzene derivatives also function as a source of phenazine mono-fV-oxides thus, if 4-chloronitrosobenzene is treated with sulfuric acid in acetic acid at 20 °C the fV-oxide is formed (Scheme 21). 

Quinoxaline and phenazine di-fV-oxides are also directly available by the Beirut reaction (see Section 2.14.3.2). 

Pyrazine and quinoxaline fV-oxides generally undergo similar reactions to their monoazine counterparts. In the case of pyridine fV-oxide the ring is activated both towards electrophilic and nucleophilic substitution reactions however, pyrazine fV-oxides are generally less susceptible to electrophilic attack and little work has been reported in this area. Nucleophilic activation generally appears to be more useful and a variety of nucleophilic substitution reactions have been exploited in the pyrazine, quinoxaline and phenazine series. 

Ring substituents show enhanced reactivity towards nucleophilic substitution, relative to the unoxidized systems, with substituents a to the fV-oxide showing greater reactivity than those in the /3-position. In the case of quinoxalines and phenazines the degree of labilization of a given substituent is dependent on whether the intermediate addition complex is stabilized by mesomeric interactions and this is easily predicted from valence bond considerations. 2-Chloropyrazine 1-oxide is readily converted into 2-hydroxypyrazine 1-oxide (l-hydroxy-2(l//)-pyrazinone) (55) on treatment with dilute aqueous sodium hydroxide (63G339), whereas both 2,3-dichloropyrazine and 3-chloropyrazine 1-oxide are stable under these conditions. This reaction is of particular importance in the preparation of pyrazine-based hydroxamic acids which have antibiotic properties. 

In the case of substituted phenazine fV-oxides some activation of substituents towards nucleophilic substitution is observed. 1-Chlorophenazine is usually very resistant to nucleophilic displacements, but the 2-isomer is more reactive and the halogen may be displaced with a number of nucleophiles. 1-Chlorophenazine 5-oxide (56), however, is comparable in its reactivity with 2-chlorophenazine and the chlorine atom is readily displaced in nucleophilic substitution reactions. 2-Chlorophenazine 5,10-dioxide (57) and 2-chlorophenazine 5-oxide both show enhanced reactivity relative to 2-chlorophenazine itself. On the basis of these observations, similar activation of 5- or 6-haloquinoxaline fV-oxides should be observed but little information is available at the present time. 

In those reactions where the fV-oxide group assists electrophilic or nucleophilic substitution reactions, and is not lost during the reaction, it is readily removed by a variety of reductive procedures and thus facilitates the synthesis of substituted derivatives of pyrazine, quinoxaline and phenazine. 

The reactions of haloquinoxalines in which the halogen atom is bonded to the benzenoid ring have not been well studied, but by analogy with examples in the phenazine series it would seem probable that they are unlikely to be displaced with the same ease as those bonded directly to the heterocyclic ring. It is evident from the foregoing discussion that A-oxidation has a pronounced effect on their reactivity, and, by this means, considerable latitude in the specific functionalization of dihalo or polyhalo derivatives may be exercised. 

Perhaps one of the most exciting developments in the chemistry of quinoxalines and phenazines in recent years originates from the American University of Beirut in Lebanon, where Haddadin and Issidorides first made the observation that benzofuroxans undergo reaction with a variety of alkenic substrates to produce quinoxaline di-AT-oxides in a one-pot reaction which has subsequently become known as the Beirut reaction . Many new reactions tend to fall by the wayside by virtue of the fact that they are experimentally complex or require starting materials which are inaccessible however, in this instance the experimental conditions are straightforward and the starting benzofuroxans are conveniently prepared by hypochlorite oxidation of the corresponding o-nitroanilines or by pyrolysis of o-nitrophenyl azides. 

The cleavage of fused pyrazines represents an important method of synthesis of substituted pyrazines, particularly pyrazinecarboxylic acids. Pyrazine-2,3-dicarboxylic acid is usually prepared by the permanganate oxidation of either quinoxalines or phenazines. The pyrazine ring resembles the pyridine ring in its stability rather than the other diazines, pyridazine and pyrimidine. Fused systems such as pteridines may easily be converted under either acidic or basic conditions into pyrazine derivatives (Scheme 75). 

Phenanthro[l,2-d][l,2,3]selenadiazole, 10,11 dihydro- H NMR, 6, 348 synthesis, 6, 353 Phenanthro[b]thiophenes synthesis, 4, 914 Phenanthro[4,5-bcd]thiophenes synthesis, 4, 883, 907, 914 Phenanthro[9,10-ej[l, 2,4]triazines synthesis, 3, 434 Phenarsazin synthesis, 1, 561 Phenazine dyes, 3, 196-197 nitration, 3, 177 UV Spectra, 2, 127 Phenazine, 3-amino-2-hydroxy-in colour photography, 1, 374 Phenazine, 1-chloro-nucleophilic substitution, 3, 164-165 5-oxide... 

W 0 H L - A U E Phenazine synthesis Synthesis of phenazine N-oxide from anilines and nitrobenzene... 

Analogous to other N-oxides of polynitrogen heterocyclic bases, quinoxaline 1-oxide and phenazine 9-oxides undergo quater-... 

A range of products was obtained from aniline including those from oxidative coupling (azozybenzene, azobenzene, and benzidine), and phenazine by dimerization (Chan and Larson 1991). Oxidation of m-phenylenediamine was initiated by the oxidation of two molecules to produce an A-phenyl-2-aminoquinone-imine that reacted with m-phenylenediamine to produce 2-amino-5-phenylaminoquinone-imine after further oxidation (Kami et al. 2000). 

The generation of other heteroq cles from Bfx and Fx has been the subject of exhaustive investigation. The most important transformation of Bfx to other heterocycles has been described by Haddadin and Issidorides, and is known as the Beirut reaction . This reaction involves a condensation between adequate substituted Bfx and alkene-type substructure synthons, particularly enamine and enolate nucleophiles. The Beirut reaction has been employed to prepare quinoxaline 1,4-dioxides [41], phenazine 5,10-dioxides (see Chap. Quinoxahne 1,4-dioxide and Phenazine 5,10-dioxide. Chemistry and Biology ), 1-hydroxybenzimidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [42], and benzo[e] [ 1,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyan-amide [43-46] (Fig. 4). 

The oxidation of N ADH has been mediated with chemically modified electrodes whose surface contains synthetic electron transfer mediators. The reduced form of the mediator is detected as it is recycled electrochemically. Systems based on quinones 173-175) dopamine chloranil 3-P-napthoyl-Nile Blue phenazine metho-sulphatemeldola blue and similar phenoxazineshave been described. Conducting salt electrodes consisting of the radical salt of 7,7,8,8-trtra-cyanoquinodimethane and the N-methylphenazium ion have been reported to show catalytic effects The main drawback to this approach is the limited stability... 

Phenazine leucos are generally more reactive and more susceptible to air oxidation than the thiazines and oxazines. Incorporation of electron-withdrawing groups on the acyl substituent at the 10-position of the leuco dye can provide a substantial improvement in the thermal and light stability of the leuco form and it is found that in general the stronger the electron-withdrawing character of the acyl substituents the more stable the leuco is.18... 

As in the case of thiazine and oxazine leuco dyes described earlier, the reductive acylation of the phenazine dye 52 results in the acylation of the exocyclic amino group.18 The phenazine leuco obtained 53 retains the exocyclic amide group on oxidation resulting in the acylated phenazine dye 54, the color of which is different from the one intended. 

The book is divided into seven chapters. Chapter 1 describes photo-chromic materials which have critical applications in memory technology. These compounds generally are activated by light. Chapter 2 covers leuco quinones which, in many cases, when oxidized, have their absorption maxima in the near-infrared region. Chapter 3 describes leuco dyes of a common group of compounds—oxazine, thiazine, and phenazines—that have found applications in color photography. Chapters 4-6 describe arylmethine-type compounds that can be triggered to dyes by common chemistry. Chapter 7 describes a special class of leuco dyes, namely, tetra-... 

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