Phenoxazine oxidation

Phenoxazine-1,9-dicarboxylie acid, 2-amino-4,6-dimethyI-3-oxo-occurrence, 3, 1037 Phenoxazines arylation, 3, 1011 electrophilic reactions, 3, 1012 nitration, 3, 1012 nomenclature, 3, 996 oxidation, 3, 1010 reactions, 3, 1011 structure, 2, 4, 7-8 3, 1010 synthesis, 3, 1033... 

Oxidation of P-nicotinamide adenine dinucleotide (NADH) to NAD+ has attracted much interest from the viewpoint of its role in biosensors reactions. It has been reported that several quinone derivatives and polymerized redox dyes, such as phenoxazine and phenothiazine derivatives, possess catalytic activities for the oxidation of NADH and have been used for dehydrogenase biosensors development [1, 2]. Flavins (contain in chemical structure isoalloxazine ring) are the prosthetic groups responsible for NAD+/NADH conversion in the active sites of some dehydrogenase enzymes. Upon the electropolymerization of flavin derivatives, the effective catalysts of NAD+/NADH regeneration, which mimic the NADH-dehydrogenase activity, would be synthesized [3]. 

Such reactions are also possible in vitro, as several mild oxidizing agents are at hand nowadays. Thus, the Dess-Martin periodinane (DMP) [50] has been proven to be a versatile and powerful reagent for the mild oxidation of alcohols to the corresponding carbonyl compounds. In this way, a series of new iodine(V)-mediated reactions has been developed which go far beyond simple alcohol oxidation [51], Ni-colaou and coworkers have developed an effective DM P-mediated domino polycy-clization reaction for converting simple aryl amides, urethanes and ureas to complex phenoxazine-containing polycycles. For example, reaction of the o-hydroxy anilide 7-101 with DMP (2 equiv.) in refluxing benzene under exposure to air led to polycycle 7-103 via 7-102 in a yield of 35 % (Scheme 7.28) [52]. 

Sutherland, J.B., Freeman, J.P, Heinze, T.M. et al. (2001) Oxidation of phenothiazine and phenoxazine by Cunninghamella elegans. Xenobiotica The Fate of Foreign Compounds in Biological Systems, 31, 799-809. 

It is interesting to compare the biphenylamine substituted compounds with the corresponding carbazoles, phenoxazines, and phenothiazines. For the triaryla-mino-based structures, the carbazole 24 has the highest oxidation potential (0.69 V vs. Ag/0.01 Ag+) [102], followed by the phenoxazine 25a (0.46 V vs. Ag/0.01 Ag+) [166]. A similar observation was made for the corresponding derivatives of 36a the phenothiazine (0.27 V vs. Fc/Fc+) and the phenoxazine (0.29 V vs. Fc/Fc+) have higher oxidation potentials than the parent compound. The carbazole 37 has an even higher oxidation potential, but in this case the oxidation is not reversible [234]. The redox properties of carbazoles are not fully understood yet. In some devices, a carbazole such as CBP (10) was used as an interface layer on the cathode side, suggesting a lower barrier for electron injection [50]. 

Oxidation of catechol with Ag20 in presence of /3-alanine methyl ester gave a phenoxazine-2,3-dione in low yield, and further condensation with o-phenylenediamine gave the pentacyclic compound 153 [78ZN(C)912],... 

For the related compounds, phenothiazine and phenoxazine, the reduced form is stable under ambient conditions and oxidation occurs in two one-electron steps. A comparison between the redox behaviour of the two compounds is best made in an antimony trichloride medium where both the radical-cation and the dication levels are stable (Scheme 6.9) [225]. In perchloric acid, phenothiazine shows reversible... 

Phenoxazines and phenothiazines (446 X = 0, S) may be oxidized to phenoxazonium and phenothiazinium salts (447 X = 0, S). Radical cations are intermediates these lose H+ to form a neutral radical followed by another electron to form the six-rr-electron system (Scheme 53). On careful oxidation, radical cations (446a) can be isolated as deep-colored crystalline salts, stable enough for X-ray analysis (80JHC1053, 81JCS(P2)852, 88CB2059). 

Phenoxazin-3-ones and phenothiazin-3-ones can be prepared by the oxidation of the parent heterocycles in acidic media, but it is often more practical to employ condensation reactions between 2-amino-phenols or -thiols and quinones. Alizarin Green G (263), for example, is obtained from the aminophenol (261) and the 1,2-naphthoquinone (262). Similarly, 2-aminothiophenols (264) and 6-chloro-2-methoxy-l,4-benzoquinone (265) afford phenothiazin-3-ones (266) bearing methoxyl groups at position 1. 

Heterocyclic substrates in SET processes have been widely studied, including the reactions of dihydronicotinamide,116 pyridine, and quinoline117 and also phenoxazine and phenothiazines.118 Phenothiazine has also been shown by ESR analysis to undergo an electron-transfer reaction with its radical cation with an appreciable 15N/14N isotope effect.119 The reaction of phenazine di-iV-oxide radical cations with hydrocarbons shows evidence of non-radical processes.120... 

Oxidation of oxalic acid with dimethyl-V,V-dichlorohydantoin and dichloroisocya-nuric acid is of first order with respect to the oxidant. The order with respect to the reductant is fractional. The reactions are catalysed by Mn(II). Suitable mechanisms are proposed.129 A mechanism involving synchronous oxidative decarboxylation has been suggested for the oxidation of a-amino acids with l,3-dichloro-5,5-dimethylhydantoin.130 Kinetic parameters have been determined and a mechanism has been proposed for the oxidation of thiadiazole and oxadiazole with trichloroiso-cyanuric acid.131 Oxidation of two phenoxazine dyes, Nile Blue and Meldola Blue, with acidic chlorite and hypochlorous acid is of first order with respect to each of the reductant and chlorite anion. The rate constants and activation parameters for the oxidation have been determined.132... 

It seems likely that aromatic amines which are found in liquefaction products have been produced by a combination of thermolysis and hydrogenation. There is no evidence for aromatic amines in coals from either selective oxidation degradations (22) or from direct X-ray Photoelectron Spectroscopy measurements (23). Oxidations would produce very stable nitroaromatics which are not seen. Another possible structure for this formula is phenoxazine(Vb). Such a molecule would not survive high temperature combined with long reaction times. Although annelated thiophene with a pyrrole(VI) would appear to be a likely structure in coal, there is no evidence for its existence in any of the coal derived materials. 

Chemically modified electrodes (CMEs) for electrocatalytic oxidation of the reduced form of the nicotinamide adenine dinucleotide cofactor (NADH) are discussed. The work of the authors in the field is reviewed. CMEs based on adsorbed polyaromatic redox mediators (phenoxazines and phenothiazines) and the deposition of aqueous insoluble redox polymers are described. 

Some of the structures reported from this laboratory for making CMEs for electrocatalytic oxidation of NADH are summarized in Figure 5. We have found that a positively charged paraphenylene-diimine is the best basic catalytic structure (55,83,84-87,89,91,92). When it is incorporated as a part of a phenoxazine or a phenothiazine (see Figure 5) some very beneficial properties are added to the mediator. The E° values are decreased with some 300 to 400 mV compared with the free paraphenylenediimine structure (57,58,102) and they strongly adsorb on graphite electrodes to form CMEs allowing NADH to be electrocatalytically oxidized well below 0 mV (55,83,84-87,89,91,92). 

The close coupling between the phenoxazine or phenothiazine modifier and a graphite electrode (E-electron overlapping) results in very fast charge transfer rates between the modifier and the electrode seen as small peak separations in cyclic voltammetry (83,86,87,92). The adsorption of the mediators also results in a further decrease in the E0 values with about 50 to 100 mV compared with the bulk values (83,84,92). Drastic changes in the pKg values of both the reduced and the oxidized forms of the adsorbed mediator have also been noticed (83,84,92). 

Figure 5. Some structural formulae of phenazine, phenoxazine, and phenothiazine mediators used at this laboratory for making CMEs used for electrocatalytic oxidation with NADH. continued on next page.

Gorton and coworkers have been particularly active in this field and produced an excellent review of the methods and approaches used for the successful chemical modification of electrodes for NADH oxidation [33]. They concentrated mainly on the adsorption onto electrode surfaces of mediators which are known to oxidise NADH in solution. The resulting systems were based on phenazines [34], phenoxazines [35, 36] and pheno-thiazines [32]. To date, this approach has produced some of the most successful electrodes for NADH oxidation. However, attempts to use similar mediators attached to poly(siloxane) films at electrode surfaces have proved less successful. Kinetic analysis of the results indicates that this is because of the slow charge transfer between the redox centres within the film so that the catalytic oxidation of NADH is restricted to a thin layer nearest the electrode surface [37, 38]. This illustrates the importance of a charge transfer between mediator groups in polymer modified electrodes. 

This type of mechanism has been proposed for a variety of different NADH oxidation systems, including phenoxazine dyes [35, 36], phenothia-zine dyes [39] and a conducting organic salt [40]. Experimental evidence for the formation of a complex during the chemical oxidation of NADH has been provided by Fukuzumi et al. [41]. These authors showed that a mixture of an NADH model compound and a quinone derivative formed a charge-transfer complex in solution as determined by UV/Vis spectros-... 

The phenoxazine radical ion was obtained in concentrated sulfuric acid with 30% hydrogen peroxide. However, phenoxazine dissolved in sulfuric acid on standing for a few days yielded an identical spectrum without addition of any oxidant. 

Lagerkrantz and Yhland51 could show that some phenoxazine dyes have an ESR absorption in the solid state even without any oxidant added. In acid solution with relatively high concentration these dyes produce a spectrum of four lines, with the line width of... 

Phenoxazines are known to be readily oxidized. According to Musso88 the first stage in the oxidation of phenoxazine with ferric... 

Phenoxazine and 3-acetoxyphenoxazine, as well as their 10-acetyl derivatives, when oxidized with nitrous acid at 5°, are converted into 3H-phenoxazin-3-ones.40... 

Friedel-Crafts reaction of -acetylphenoxazine in carbon disulfide with a large excess of acetyl chloride and aluminum chloride yielded 2,8-diacetylphenoxazine (28), which proved to be identical with the diacetylphenoxazine which was formed by oxidation of 2,8-diethyl-phenoxazine with potassium permanganate (see Section IV,E).61... 

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