Oxidation of carbazoles

Resnick SM, DS Torok, DT Gibson (1993) Oxidation of carbazole to 3-hydroxycarbazole by naphthalene 1,2-dioxygenase and biphenyl 2,3-dioxygenase. FEMS Microbiol Lett 113 297-302. 

A species believed to be the monomer cation radical of 9-ethylcarbazole as a green solution in acetonitrile formed by oxidation of 9-ethylcarbazole with iodine-silver(I) perchlorate, was detected by ESR spectroscopy, although the perchlorate of the cation radical could not be isolated subsequent treatment with potassium iodide gave 9,9 -diethyl-3,3 -bicarbazole. The borofluoride salts generated as crystalline materials by oxidation of carbazole or 9-methylcarbazole with tropylium borofluoride in acetonitrile followed by precipitation with methanol are not salts of the monomer cation-radicaP as originally believed. Russian workers have suggested that nitration of carbazole proceeds via a cation radical. ... 

Nitrosocarbazole condenses with 9-aminocarbazole to give the azo compound 122, heating of which produces dimers in a ratio similar to that observed by oxidation of carbazole (see Section II,A,2) it was therefore believed to involve the carbazol-9-yl radical. 3-Nitro-9-nitrosocarbazole was shown to serve as a nitrosating agent for A-methylaniline it converted aziridine to ethene and nitrous oxide. ... 

Electrochemical and spectroscopic techniques have been used to study the oxidation of carbazole and 71 of its derivatives.207,208 Positions 3, 6, and 9 of the carbazole nucleus are the most reactive sites, as expected from Hiickel theory. The products isolated are symmetric carbon-carbon (3,3 ) and nitrogen-nitrogen (9,9 ) dimers. Substitution of carbazoles in the 3-, 6-, and 9-positions prevents anodic dimerization at these positions the electrochemical formation of a stable radical-cation is possible.209 The electrochemical oxidation of iminobibenzyl and several related compounds have been investigated in CH3CN-Bu4NC104 and their electrochemistry was compared with that of related carbazoles.210... 

Considerably fewer studies Have been made of the analogous oxidations of carbazoles and there appears to be some ambiguity in the data. It is probable that the major product... 

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). 

The formation of cation-radicals by carbazoles is well documented. In 1968, it was observed that oxidation of carbazoles with lead tetraacetate in acid conditions led to the formation of the cation-radical of the corresponding 3,3 -dicarbazole. The radicals are persistent and uninfluenced by air or water.466 This work was subsequently pursued further, and similar oxidations were effected by other typically single-electron oxidants.467 Indications from electrochemical work that the simple cation-radicals are the reactive intermediates appeared about the same time as the initial observation.468 This work, too, has been followed-up in depth. Electrochemical... 

A. Desbenemonvemay, P. C. Lacaze, J. E. Dubois, Polaromicrotribometric (PMT) and IR, ESCA, electron-paramagnetic-res spectroscopic study of colored radical films formed by the electrochemical oxidation of carbazoles. 1. Carbazole and N-ethyl, N-phenyl and N-carbazyl derivatives, /oMr a/ of Electroanalytical Chemistry 1981, 129, 229. 

A similar mechanism has been found in the case of other polyheterocycles. For example, the deposition of polycarbazole has been shown to involve the initial formation of cation radicals. The electrooxidation of carbazole in the nonaqueous medium was thoroughly studied by Ambrose and Nelson [10], who established that a dicarbazyl radical resulting from the coupling of carbazole cations at the 3-position is formed. These authors did not report polymerization of carbazole. However, others who have investigated the oxidation of carbazole [11] reported polymerization. An iodinated, chemically polymerized material was also reported [12]. The mechanism for the formation of polycarbazole in dimethyl formamide (DMF) or aqueous medium is shown in Scheme 2 [11]. 

FIGURE 1 Cyclic voltammogram for the oxidation of carbazole (60 mM) in DMF/O.I M tetra-/i-butyl ammonium perchlorate medium. Scan rate 140 mV/s. Working electrode Pt wire. Potentials referred to Ag wire quasi-reference electrode. (Data from Ref. 11.)... 

Examples include luminescence from anthracene crystals subjected to alternating electric current (159), luminescence from electron recombination with the carbazole free radical produced by photolysis of potassium carba2ole in a fro2en glass matrix (160), reactions of free radicals with solvated electrons (155), and reduction of mtheiiium(III)tris(bipyridyl) with the hydrated electron (161). Other examples include the oxidation of aromatic radical anions with such oxidants as chlorine or ben2oyl peroxide (162,163), and the reduction of 9,10-dichloro-9,10-diphenyl-9,10-dihydroanthracene with the 9,10-diphenylanthracene radical anion (162,164). Many other examples of electron-transfer chemiluminescence have been reported (156,165). 

In Europe, where an abundant supply of anthracene has usually been available, the preferred method for the manufacture of anthraquinone has been, and stiU is, the catalytic oxidation of anthracene. The main problem has been that of obtaining anthracene, C H q, practically free of such contaminants as carbazole and phenanthrene. Many processes have been developed for the purification of anthracene. Generally these foUow the scheme of taking the cmde anthracene oil, redistilling, and recrystaUizing it from a variety of solvents, such as pyridine (22). The purest anthracene may be obtained by azeotropic distillation with ethylene glycol (23). 

The DszC enzyme was able to convert the following compounds other than DBT thioxanthen-9-one, 2,8-dimethyl DBT, 4,6-dimethyl DBT, and 3,4-benzo DBT. Non-organosulfur compounds such as biphenyl, carbazole, and dibenzofuran did not show any activity. This indicates that dszC specifically recognizes sulfur atom [151]. One study specifically examined the DszC enzyme for oxidation of aryl sulfides [179] and reported oxidation of many sulfides including, naphthyl methyl sulfide, phenyl methyl sulfide, and its alkyl derivatives. 

In conclusion, the fantastically diverse chemistry of indole has been significantly enriched by palladium-catalyzed reactions. The accessibility of all of the possible halogenated indoles and several indolyl triflates has resulted in a wealth of synthetic applications as witnessed by the length of this chapter. In addition to the standard Pd-catalyzed reactions such as Negishi, Suzuki, Heck, Stille and Sonogashira, which have had great success in indole chemistry, oxidative coupling and cyclization are powerful routes to a variety of carbazoles, carbolines, indolocarbazoles, and other fused indoles. 

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]. 

Proximity effects and ortho interactions in 2,2/-disubstituted diaryl amines have been reported104. Thus, phenazine, phenazine-N-oxide and carbazole were formed by loss of small neutral fragments, such as NO, NO2 and NO3, from the molecular ions, as illustrated by the formation of carbazole from 2,2/-dinitrodiphenylamine see Scheme 34. Of particular interest is the loss of NO3, as demonstrated by high-resolution MS data and metastable ion spectra104. 

Convergent Synthesis of Carbazoles by Oxidative Coupling of Arylamines. .. 121... 

Scheme 8 Synthesis of carbazoles by oxidative coupling of arylamines...

A molybdenum-mediated oxidative coupling of aniline 1 with cyclohexene 2a provides carbazole 3. Alternatively, the same overall transformation of aniline 1 to carbazole 3 is achieved by iron-mediated oxidative coupling with cyclo-hexa-1,3-diene 2b or by palladium-catalyzed oxidative coupling with arenes 2c. The use of appropriately substituted anilines and unsaturated six-membered hydrocarbons opens up the way to highly convergent organometallic syntheses of carbazole alkaloids. 

The molybdenum-mediated arylamine cyclization was also applied to the total synthesis of pyrano[3,2-a]carbazole alkaloids (Scheme 26). Reaction of the 5-aminochromene 71 with the complex salt 62 affords the complex 72, which on oxidative cyclization provides girinimbine 73, a key compound for the transformation into further pyrano[3,2-a] carbazole alkaloids. Oxidation of 73 with DDQ leads to murrayacine 74, while epoxidation of 73 using meta-chloro-perbenzoic acid (MCPBA) followed by hydrolysis provides dihydroxygirinim-bine75 [113]. 

The palladium(II)-mediated oxidative cyclization is also applied to the synthesis of carbazole-l,4-quinone alkaloids. The required arylamino-l,4-benzo-quinones are readily prepared by arylamine addition to the 1,4-benzoquinone and in situ reoxidation of the resulting hydroquinone [131]. 

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