Indoles anodic oxidation

Pyrrole derivatives substituted in positions 1-, 3-, or 4- have also been electrochemically polymerized (positions 2- and 5- must be free for polymerization). Besides homopolymers, copolymers can also be prepared in this way. Other nitrogen heterocycles that have been polymerized by anodic oxidation include carbazole, pyridazine, indole, and their various substitution derivatives. 

Guertler et al. (1996) described a wide range of cycloaddition reaction between 2-vinyl indoles acting as heterodienes and cyclic or acyclic enamines bearing acceptor groups in (3 positions. The reaction was induced by the formation of 2-vinylindole cation-radicals through anodic oxidation. The synthesis of 4a-carbomethoxy-6-cyano-5,7-dimethylindolo[l,2-a]-l,2,3,4,4a,12a-hexahydro-1,8-naphthyridine can serve as an example (Scheme 7.24). 

Electron donating a-substituents favour the non-Kolbe reaction but the radical intermediates in these anodic processes can be trapped during co-electrolysis with an alkanoic acid. Anodic decarboxylation of sugar uronic acids leads to formation of the radical which is very rapidly oxidised to a carbonium ion, stabilised by the adjacent ether group. However, in the presence of a tenfold excess of an alkanoic acid, the radical intermediate is trapped as the unsymmetrical coupling product [101]. Highly functionalised nucleotide derivatives such as 20 will couple successfully in the mixed Kolbe reaction [102], Other examples include the co-electrolysis of 3-oxa-alkanoic acids with an alkanoic acid [103] and the formation of 3-alkylindoles from indole-3-propanoic acid [104], Anodic oxidation of indole-3-propanoic acid alone gives no Kolbe dimer [105],... 

The electrochemical generation of a nitrilimine provides an entrance to a wide range of heterocyclic systems via anodic oxidation of aldehyde hydra-zones. The same reaction was used for annelation of various heterocyclic systems,86 e.g., substituted pyridines, quinolines, isoquinolines, indoles, imidazoles, benzimidazoles, and benzotriazoles. 

The evidence for transient radical-cations from N-substituted indoles has been furnished by the observation of regiocontrolled anodic cyanation of the indole ring.193,194 Substitution in the 2-position dominates, although some 3-substitution takes place. When the 1,2,3-positions of indole were blocked, no cyanation occurred, but the products of anodic oxidation have not been isolated.194... 

A key intermediate for the synthesis of the indole alkaloid, vineamine, has been prepared by the anodic oxidation of l-earbomethoxy-3-ethyl-3-(P-carboxyethyl)-piperidine 33 in methanol. The regioselective methoxylation at the 2-position was not possible, instead the 6-position was also methoxylated. Thus, the starting material has been methoxylated at both 2- and 6-positions to give 34 and the methoxy group on the 6-position is eliminated during the formation of lactone ring at the 2-position24). 

An enamine (4) prepared from aniline and an aromatic ketone yields indole-type compounds (5 and 6) upon anodic oxidation (equation 3)4. 

Recently, evidence for the transient ex istence of cation-radicals from simple pyrroles and indoles has been furnished by the observation of anodic regiospecific cyanation of these heterocycles.455 Both heterocycles are preferentially cyanated at the 2-position. Methyl side chains at these positions are also activated to cyanation and deuteration. Indole cation-radicals have been generated by photoionization in an aqueous medium.456 Unsubstituted at N, their lifetime in neutral solution is 10-6sec before they lose the N-proton however, it is longer in more acidic conditions.456 The photophysical properties of indole, its cation-radical, and neutral radical have been the subject of a recent theoretical analysis.457 On anodic oxidation of 2,3-diphenyl indole in acetonitrile, the initially formed cation-radicals dimerize to a product identified, primarily on the basis of 13C NMR, as 3-(5-indolyl)-indolenine (141).458... 

The direct synthesis by anodic oxidation of a new series of electrically conducting poljnners is described.. Our polymers derive from sulfur and/or nitrogen containing hetero-cycles such as 2-(2-thienyl)pyrrole, thiazole, indole, and phthalazine. The anodic oxidation of these monomers is carried out in acetonitrile solutions containing tetrabu-tylammonium salts (TBA X ) ith X = BF, tetraethylammonium salt, TEA H C-C H -S0. Characterization of the materials by electrical conductivity, electron spin resonance, uv-visible spectroscopy, and cyclic voltammetry is discussed. 

Intramolecular cyclization is a general reaction in the anodic oxidation of substituted amino alkenes. Thus, the already mentioned A-methyl-A-phenyl-1,2,2-triphe-nylvinylamine leads to a new 3/7-indole by anodic oxidation in the presence of 2,6-lutidine [149,150]. The corresponding enediamine undergoes an electrolytic double cyclization to form an indolooxazolidine [149]. The formation of isoquinolines, benzaze-pines, and tetrahydrocarbazoles may also be obtained by anodically initiated intramolecular cyclization of A-benzyl, A- S-phenethyl, and anilino enaminones [Eq. (30)] [158]. 

Formation of a cation radical of the diene may catalyze Diels-Alder reactions with certain dienophiles thus oxidation of substituted vinylindoles to the cation radical in the presence of a push-pull dienophile may form different heterocyclic compounds by the Diels-Alder reaction, for instance pyrido[l,2i7]indoles from vinylindoles and yS-enamino-esters [33]. Similarly, anodic oxidation in MeCN of certain oxazolidines in presence of vinyl ether leads to derivatives of oxazepines in a catalytic reaction in which the ring-opened radical cation of the oxazolidine adds to the vinyl ether and the radical cation of the resulting oxazepine oxidizes the oxazolidine [34]. 

The initial attack in the anodic oxidation of papaverine [75] probably involves a similar attack further oxidation and dimerization leads to the isolated product, 12,12 -bis-(2,3,9,10-tetramethoxyindolo[2,l-fl]isoquinolyl). An analogous reaction is the electrooxidation of a tetramethoxy-substituted 2-methyl-l-phenethyl-l,2,3,4-tetrahydroisoquinoline to a dibenzoquinolizinium derivative [76] and the oxidation of A,A -triphenyl-( -phenyle-nediamine to 9,10-diphenylphenazine [77]. Intramolecular Michel addition of nitrogen in a tetrahydroquinoline derivative to an o-quinone moity have resulted in the formation of a 5,6-dihydrodibenz[6,d]indolizine derivative [78]. A similar ring closure occurs during the oxidation of various catecholamines [79] and similar compounds [79] to indoles. Cyclic a-carbonylazo compounds, generated by anodic oxidation of the hydrazines, may be trapped by reaction with dienes to the expected heterocycles [80]. 

Pyrrole is not polarographically reducible but can be reduced at a lead cathode in dilute sulfuric acid to pyrroline and further to pyrrolidine [203]. Under similar conditions 1,2-dimethylpyrroline [204] is also reduced to the pyrrolidine and indoles [205-207] to indo-lines or dimerized products [208]. 1-Methylindole can be reduced to 2,3-dihydro-1-methyl-indole in aqeuous THE at very negative potentials using TBAOH as electrolyte [209]. Pyrrole may also be oxidized anodically oxidation of pyrrole may result in the formation of polypyrrole useful for preparation of conducting polymers (Chapter 32). 

Diphenylindole forms, on anodic oxidation, a cation radical that dimerizes the dimer is probably of the indole-indolenine type [217, 218], dimerized at C3-C6 [219] rather than at C3-C5 [220, 221]. The reaction is similar to the oxidation of 1,2,3,4-tetra-hydrocarbazole [222]. 

Trifluoromethyl-indoles can be prepared in a similar manner as shown in Eq. 64. In this case, anodic oxidation provides p-benzo-quinone imine derivatives 29, which are easily converted into trifluoromethyl-indoles 30 by heating or by treatment with ceric ammonium nitrate. 

Yoshida s cation pool method is also applicable to the coupling of aromatics (Scheme 8.56). The radical cation pool (112), which is generated by the anodic oxidation of naphthalene and pyrene, has been added to a variety of aromatics such as substituted benzenes and indoles to provide the CDC products (113) in good yields. 

Indium-tin-oxide anode, 22 215, 216 Indium trichloride, 14 197, 201 Indo-3-lyl acetic acid, 13 284 Indole-3-acetic acid, 13 35, 38. See also Indoleacetic acids (IAAs) Indole-3-butyric acid, 13 25t... 

Keech, P. G. and Bunce, N. J. (2003) Electrochemical oxidation of simple indoles at a Pb02 anode. J. Appl. Electrochem. 33, 79-83. 

Polypyrrole degradation (pyrolysis at 600°C or anodic over-oxidation) gave benzene, indole, carbazole, etc. fragments. 

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