Nitrones electrochemical oxidation

Continuing his studies on the metallation of tetrahydro-2-benzazepine formamidines, Meyers has now shown that the previously unsuccessful deprotonation of 1-alkyl derivatives can be achieved with sec-butyllithium at -40 °C <96H(42)475>. In this way 1,1-dialkylated derivatives are now accessible. The preparation of 3//-benzazepines by chemical oxidation of 2,5- and 2,3-dihydro-l/f-l-benzazepines has been reported <96T4423>. 3Af-Diazepines are also formed by rearrangement of the 5//-tautomers which had been previously reported to be the products of electrochemical oxidation of 2,5-dihydro-lAf-l-benzazepine <95T9611>. The synthesis and radical trapping activities of a number of benzazepine derived nitrones have been reported <96T6519, 96JBC3097>. 

In electrochemical oxidation of l-hydroxy-3-imidazoline-3-oxides containing one to four H atoms at a-C, one observes in ESR-spectra not only triplet splitting of the nucleus 14N of the nitroxyl group (a v 15-16 G) but also splitting of the neighboring protons (a// 18-20 G), with multiplets corresponding to their number (from doublet to quintet) (101). Unlike spatially hindered hydroxylamines which show reversibility in electrochemical oxidation, hydroxylamines with H at a-C are oxidized irreversibly. Oxidation of hydroxylamines with nitroxyl radical proceeds easily and with quantitative yields (102). In the oxidation of asymmetric polylluorinated hydroxylamines with Mn02, isomeric polyfluorinated nitrones have been obtained (103). 

To undertake oxidation of both cyclic and acyclic hydroxylamines to nitrones, an electrochemical oxidative system has been developed, where WC>42-/WC>52-are used as cathodic redox mediators and Br /Br2 or I—/I2 as anodic redox mediators (129-131). 

Unlike the 4H- imidazoles (219), (223), (224) electrochemical oxidation of the nitrone group in 4-R-3-imidazoline-3-oxides (228), (230-232), as in a-PBN and DMPO is of irreversible nature. Therefore, the formation of radical cations... 

Determination of electrochemical oxidation potentials and electrochemical reduction of 13 p-phosphorylated acyclic nitrones shows that phosphorylated compounds have a clear anodic shift of potentials of both, oxidation (Ep 1.40 to 2.00 V versus SCE in CH3CN) and reduction (Ep—0.94 to —2.06 V). This is caused by a strong electron-acceptor influence of the diethoxyphosphoryl group (430). In contrast, a reversible one-electron oxidation of azulene nitrones (233) (Scheme 2.80) occurs 0.6 V below the Ep potential of PBN, that is at the value one observes the oxidation of AH -imidazole-1,3-dioxides (219) (428, 429). In other words, the corresponding RC (234) is 14 kcal more stable than the RC of PBN. Although the EPR spectrum of RC (234) was not recorded, RC (236) from dinitrone (235) turned out to be rather stable and gave an EPR spectrum (170). 

Nitrones were prepared by the electrochemical oxidation of N-hydroxy secondary amines using a supporting electrolyte such as... 

In the series of a-substituted nitrones, the a-methoxy nitrones are the most easily oxidized nitrone derivatives. The study of electrochemical behavior of acyclic a-methoxy-, a-amino-, a-cyano- and a-mercapto-nitrones has shown an irreversible one-electron oxidation of the nitrone group (429). 

The initially formed nitronate radical reacts with olefin R C=CR" to give an elongated radical A whose successive cyclization and oxidation affords target nitronates (5g) in 18% to 81% yields. Manganese triacetate is regenerated by electrochemical methods. 

Addition of carbanions (which may be electrochemically generated), derived from active methylene compounds (such as fluorene or indene193), to nitrosobenzene produces the intermediate181 70, which is dehydrated to the azomethine 71 or may be oxidized to the nitrone derivative 72, as illustrated by Scheme 8. 

The N-oxide moiety in heterocyclic amine N-oxidcs, like QDO and PDO, presents a particular electrochemical behavior. On the one hand, the oxygen N-oxide atom could suffer loss of one electron, an oxidation process, and on the other hand, the nitrogen N-oxidc atom, like in nitro compounds or nitrones, could receive one electron in a reduction pathway (Scheme 3). Both processes conduct to different reactive entities that have been studied using different electrochemical and spectroscopic techniques. 

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