Amides electrochemical oxidation

The electrochemical oxidation of cyclic and acyclic, V-monosubstitilted and ATY-disubstituted amides and carbamates in a nucleophilic solvent, known as the Ross-Eberson-Ny berg reaction, is a synthetically very useful, clean and efficient method for the introduction of a-oxygen substituents under mild reaction conditions6 1 0. 

Various oxidations of amides or carbamates can also generate acyliminium ions. An electrochemical oxidation forms a-alkoxy amides and lactams, which then generate... 

Eberson and Olofsson, 4> observed exactly the same effect, and advanced the same rationale, in their study of the electrochemical oxidation of 5 in acetonitrile-water mixtures, to afford mixtures of pentamethylbenzyl alcohol (10) and the amide 9. 

Amines are stable to electrochemical oxidation in acid solution because the nitrogen lone pair is protonated and inaccessible for reaction. This is not the case for N-acetylamines, which are oxidisable at a lead dioxide anode in aqueous sulphuric acid [99]. The primary electron tiansfer step involves the amide function and leads to a radical-cation, which loses a proton from the carbon atom adjacent to nitrogen. Subsequent steps lead to an acylimmonium ion, which is trapped by water. N-acetylated primaiy amines are converted to the corresponding carboxylic acid. 

Early workers noted that electrochemical oxidation of N,N-dimethyl-amides in acetic acid gives the a-acetoxy compound [101]. Oxidation in acetic acid of amides derived from piperidine and pyrroUdine proceeds differently to yield a mixture of stereoisomers of the a,P-diacetoxy and p-acetoxy-a-hydroxy compounds [125]. 

Electrochemical oxidation of hydroxamic acids in the presence of amines, alcohols or water afforded the corresponding amides, esters or carboxylic acids (equation 19) . ... 

This electrochemical oxidation mediated by NHPI was applicable to benzylic carbons, allylic carbons, deprotection of acetals, oxidative cleavage of cyclic acetals and amide to afford benzoylated compounds, enones ", carbonyl compounds, -hydroxyethyl esters and imides, respectively (equations 31-35). 

Various oxidations of amines can also generate acyliminium ions. The methods most used in synthetic procedures involve electrochemical oxidation to form z-alkoxy amides and lactams, which then generate acyliminium ions.108 Acyliminium ions are sufficiently electrophilic to react with enolate equivalents such as silyl enol ethers109 and enol esters.110... 

The electrochemical oxidation of acyl silanes has been investigated, giving rise to esters and amides when carried out in the presence of alcohols and amines. The oxidation potentials of acyl silanes proved to be much lower than those of the corresponding ketones213. 

Shono and others have shown that electrochemical oxidation of amides in nucleophilic media results in incorporation of the nucleophile into the alpha-position of the N-alkyl group via an intermediate iminium species (equation 36). This so-called anodic alpha-functionalization reaction has been shown to be of considerable synthetic value. The reaction has been extensively reviewed98. 

Aminyl radicals also can be generated via electrochemical oxidation of amide bases or O-substituted hydroxylamines. Suginome has studied radical cyclizations involving oxidations of lithium alkenylamides as a route to ccs-l-methyl-2,5-disubstituted pyrrolidines (85TL6085). Electrolysis of lithium alkenylamide 17a, generated from the amine and butyllithium at - 78°C, led to the formation of 18a, exclusively cis, in 52% yield (Scheme 4). The reactions require 0.25 M UC104 in THF HMPA (30 1) as the supporting electrolyte. A variety of 2-substituted amines were studied. 

The use of electrochemical oxidations of amides and carbamates as a key step in the synthesis of alkaloidal compounds has been recently reviewed by Shono [271]. 

Otherwise, lithium amides of secondary amines undergo anodic dimerization to form hydrazines in moderate yields [12]. Hydrazines are also generated, if secondary amines are electrochemically oxidized in the presence of an alkali hydroxide [27,28]. This reaction is mainly effective if the coupling takes place intramolecularly to give cyclic hydrazine derivatives [28]. If lithium amides of secondary amines are anodically oxidized in tetrahydro-furan (THF) solution in the presence of the free amine, 2-aminotetrahydrofurans are formed in reasonable yields. In contrast, the respective aminomagnesium bromides only gives A, A -coupling products [29]. 

The synthesis of alkaloids lupinine (106) and epilupinine (107) (Scheme 10) nicely illustrates the methodology [25]. Thus, electrochemical oxidation of lactam 103 (constant current, 50 mA Pt/Pt, Et4NC104) in methanol at room temperature afforded a 71% yield of ether 104 after the passage of 2.8F/mol. Subsequent treatment with titanium tetrachloride affected cyclization to the [4.4.0] bicyclic adduct 105. Krapcho decarbomethox-ylation followed by hydride reduction of both the amide and ester units of the resulting epimeric esters provided the natural products 106 and 107. 

The oxidation of N-monosubstituted 3-amino-2-aryl-thioacrylic acid-morpholides 20 using hydrogen peroxide in perchloric acid gave 5-morpholino-isothiazolium perchlorates2 21a,c-g (83JPR689) in good yields (Scheme 4). The electrochemical oxidation of 3-amino-thioacryl acid-amides 20 (R = CH2C02Me) is a useful... 

Decarbonylation from acyl radicals is a serious side reaction in the reaction of tellurol esters bearing secondary and tertiary alkyl carbon units as R. However, decarbonylation can be avoided by carrying out the reaction under CO pressure. In addition, electrochemical oxidation of the product 102 in the presence of water afforded the corresponding a-acyl amide in quantitative yields. 

Randriamahazaka, H., Plesse, C., Teyssie, D., and Chevrot, C. (2004). Ions transfer mechanisms during the electrochemical oxidation of poly(3,4-ethylenedioxythiophene) in l-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)amide ionic liquid, Electrochem. Commun., 6, pp. 299-305. 

Scheme 6, equation 2) [12], The key step in Clive s sequence is the Hoftnann rearrangement of amide 17 to amine 18, followed by oxidation to quinone 19 with phenyliodme(ni) bis(triacetate). In like fashion, 4-bromo-5-hydroxyindole, 5-hydroxy-4-iodoindole, and 5-hydroxy-4-iodo-3-methylindole were prepared in this study. Nishiyama and coworkers adopted an electrochemical oxidation of diaryl amides to carbazoles (equation 3 and 21-22) [13]. 

Electrochemical oxidation of N-subst. carboxylic acid amides 5,6-Dihydro-l,3-oxazinium salts from ethylene derivs. 

Electrochemical oxidation in methanol gives the a-methoxy-amides and -carbamates, which afford the enamine derivatives on elimination of methanol [equation (14)]. Enehydrazides may be prepared simply by A-acylation of N N -[Pg.62]

Nyokong et al. [125] reported on hybrid materials composed of Ni(II)-3 covalently linked to SWCNT via the formation of amide bonds, for the electrocatalytic oxidation of 2-ME. The electrochemical oxidation of 2-ME studied by cycUc voltammetry in acidic medium (buffer pH 4) was observed at 0.9 V versus Ag/AgCl, the catalytic effect being attributed to Ni(III)-3 species. Upon cycling in 2-ME solution, a slight decrease of the anodic peak was observed due to the formation of adsorbed oxidized species (disulfide). Further studies of analytical... 

Goran, J. M., Favela, C. A., and Stevenson, K. J. 2013. Electrochemical oxidation of dihydronicotm-amide adenine dinucleotide at nitrogen-doped carbon nanotube electrodes. Anal. Chem. 85 9135-9141. 

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