Phenothiazines radicals from

Carbazole, like most aromatic amines, oxidizes readily via electron transfer. We recognized early that electron transfer may be an important initiation process for polymerizing the N-vinyl derivative. Some years ago we showed (29) that cycloheptatrienyl cation could act as an efficient one-electron transfer reagent, producing the appropriate cation radicals from reactive amines such as phenothiazine and tetramethyl-p-phenylene-diamine. It was also suggested that the product of the reaction between cycloheptatrientyl cation and carbazole itself was the carbazole cation radical. However, our recent work (21) has demonstrated that one-electron oxidation of carbazole leads directly to the 3,3-dicarbazoyl cation radical (VII). 

By the sodium mirror technique, Bruin et obtained in dioxan anion radicals from 3,7-diaminophenothiazine (Lauth s violet), from 3,7-bis-dimethylaminophenothiazine (methylene blue), from 7-di-methylaminophenothiazone (methylene violet), and from phenothiazine itself. From the very well resolved ESR spectra of these radicals the value x 7 G was derived. 

Chignell CF, Motten AG, Buettner GR. Photoinduced free radicals from chlorpromazine and related phenothiazines relationship to phenothiazine-induced photosensitization. Env Health Perspect 1985 64 103-110. 

A ring carbon can also be involved, however, as in the reaction of the thianthrene and phenothiazine radical cations in neat pyridine or with pyridine in an anhydrous solvent. In this reaction the 1-pyridinium group is inserted on to the benzo ring (43), apparently via nucleophilic attack on di-cations 42, in turn resulting from oxidation of the initially formed radical cation adducts (Scheme 27). In the presence of moisture the sulfoxides are again formed [84]. 

The important drugs derived from phenothiazines are substituted at N by a functionalized alkyl side chain. The cation-radicals from these materials have been the subject of various ESR investigations " those of Fenner have been the most extensive. He has partially analyzed the ESR spectra of several drugs with substituents at C-2. The hyperfine split-... 

Phenothiazine radicals have been generated in various radiolytic experiments. Pulse radiolysis of phenothiazine in aerated cycloalkane solutions gives rise to phenothiazinyl (251). ° The mode of oxidation is believed to involve abstraction of H from the heterocycle by cycloalkylperoxyl radicals. Under similar conditions, 10-methylphenothiazine gives 261. Pulse radiolysis of phenothiazine in acetonitrile has also been documented. The reduction of phenothiazine dyes under radiolytic conditions has been reported. Several years ago, Ayscough and Thomson obtained paramagnetic products from X-irradiation of acid alcoholic solutions of Methylene Blue and other thiazine dyes. Low-resolution ESR spectra of the corresponding cation-radicals were recorded. 

There is some controversy over the oxidizing properties of thiylperoxyl radicals. Thus the present author measured the rate of oxidation of the phenothiazine, chlorpromazine (CPZ) by thiyl radicals (from GSH) in the absence and presence of oxygen [109] ... 

Other reducing agents such as N2H4, NaBH4, EDTA, C2O4, and solvated electrons can be used. Chemiluminescence can be observed from the reduced form Ru(bpy)3 by the addition of oxidants such as the 10-methyl phenothiazine radical... 

One of numerous examples of LOX-catalyzed cooxidation reactions is the oxidation and demethylation of amino derivatives of aromatic compounds. Oxidation of such compounds as 4-aminobiphenyl, a component of tobacco smoke, phenothiazine tranquillizers, and others is supposed to be the origin of their damaging effects including reproductive toxicity. Thus, LOX-catalyzed cooxidation of phenothiazine derivatives with hydrogen peroxide resulted in the formation of cation radicals [40]. Soybean LOX and human term placenta LOX catalyzed the free radical-mediated cooxidation of 4-aminobiphenyl to toxic intermediates [41]. It has been suggested that demethylation of aminopyrine by soybean LOX is mediated by the cation radicals and neutral radicals [42]. Similarly, soybean and human term placenta LOXs catalyzed N-demethylation of phenothiazines [43] and derivatives of A,A-dimethylaniline [44] and the formation of glutathione conjugate from ethacrynic acid and p-aminophenol [45,46],... 

Preparative scale electrochemical oxidation of phenothiazine in aqueous acetonitrile, with no added acid, leads to the radical formed by proton loss from the radical-cation. The radical dimerizes and further oxidation leads to the green qui-nonoid cation 67 [230]. 

The advantage of using free radical inhibitors to facilitate the copolymerization of a bisbenzocyclobutene with a bismaleimide was first noted in a patent to Bartmann [78]. Subsequent to this, Corley in a series of patents described some detailed experiments on the copolymerization of bisbenzocyclobutenes with bismaleimides both with and without the addition of a free radical inhibitor [33, 34]. The structures of the bisbenzocyclobutenes used in this study are shown in Fig. 33. The bismaleimide component that was used was a mixture of three different bismaleimides in the molar ratio shown in Fig. 34. The individual bisbenzocyclobutenes were blended at elevated temperature with varying amounts of the bismaleimide composition. In some of the experiments, the free radical inhibitor phenothiazine was added at a 0.5 mole % level. The various monomer mixtures were then copolymerized using one of the cure schedules described in Table 14. The copolymers were then physically characterized using a variety of techniques. Table 14 shows the results obtained from copolymers... 

Various phenothiazines (176) have been oxidized in CH3CN-Et4NC104 to a stable radical-cation (R = OCH3). The free radical resulting from deprotonation of the radical-cation gives in those cases where R = H, SCN, or t-Bu a C—N bond dimer, possibly 177272,2-73 [Eq. (107)]. 

It is known from electrochemical studies that fullerenes are easily reduced. Up to 6 electrons can be added reversibly [19], and, as mentioned earlier, the excited states are even more easily reduced. A large number of electron donors were investigated including aromatic and alkyl amines [29,43,79,119-140,152,161], ni-troxide radicals [57,117], suspensions of Ti02 [118], polyaromatic compounds, [19,127] organo-silicon compounds, [133,158] phenothiazine, [133] acridine [145,154], (3-carotene [141], tetrathiafulvalenes [146], tetraethoxyethene [147], phthalocyanines [148], porphyrines [151,153], NADH and analogues [150,154, 155], borates [156,159], and naphtoles [23] to name a few representative cases. 

Chlorpromazine [2-chloro-A-(3-dimethylaminopropyl)phenothiazine] is a frequently prescribed antipsychotic drug which causes both phototoxic and photoallergic reactions [49,50], UV irradiation of chlorpromazine (C1PZ) in solution is known to produce the chlorpromazine cation radical [51], as well as other photoproducts, which may go through radical intermediates [52], Under UV irradiation, the aryl radical resulting from dechlorination of chlorpromazine has been trapped using 2-methyl-2-nitrosopropane (MNP),... 

Various compounds were shown to sensitize the photochemical decomposition of pyridinium salts. Photolysis of pyridinium salts in the presence of sensitizers such as anthracene, perylene and phenothiazine proceeds by an electron transfer from the excited state sensitizer to the pyridinium salt. Thus, a sensitizer radical cation and pyridinyl radical are formed as shown for the case of anthracene in Scheme 15. The latter rapidly decomposes to give pyridine and an ethoxy radical. Evidence for the proposed mechanism was obtained by observation of the absorption spectra of relevant radical cations upon laser flash photolysis of methylene chloride solutions containing sensitizers and pyridinium salt [64]. Moreover, estimates of the free energy change by the Rehm-Weller equation [65] give highly favorable values for anthracene, perylene, phenothiazine and thioxanthone sensitized systems, whilst benzophenone and acetophenone seemed not to be suitable sensitizers (Table 5). The failure of the polymerization experiments sensitized by benzophenone and acetophenone in the absence of a hydrogen donor is consistent with the proposed electron transfer mechanism. 

Similarly, phenothiazine may be oxidized to the cation radical species which then dimerizes forming the 3,10 -diphenothiazinyl species (Tsujino, 1969). The product of the electron-transfer step may react, via a second-order process, with a species in solution to form a new product. An example of this type of mechanism involves the reduction of anthraquinone and its derivatives in the presence of oxygen (Jeziorek etal., 1997). To understand quantitatively an EC and EC2 process, the concentration and scan-rate dependence of the associated cyclic voltammograms is matched with theory deriving from the mass transport/kinetic equations for each species. 

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