Pyridines anodic reactions

Anodic inhibitors limit the oxidation of iron by sharing the lone pair electrons on the nitrogen with a metal ion or atom and supressing the anodic reaction. Examples are benzotriazole (at high concentrations), pyridines, thiols, and quinolines. 

Less than 10% of the reports on pyridine electrochemistry deal with anodic reactions. The mechanisms of these reactions are rarely known and, as a result, yields or current efficiencies have not always been optimized. Many of the anodic reactions were studied in beaker cells, which are simply not good models for modern flow cells moreover, uncontrolled power supplies were often used. Consequently, anode overpolarization caused ring degradation in many cases. 

Oxidative reactions of pyridines are commercially more interesting than reductive ones because catalytic hydrogenation of pyridines is a generally useful method, whereas catalytic oxidation is not. In contrast, anodic oxidation of pyridines is widely applicable and can replace methods that use expensive oxidants such as permanganate salts or chromic oxide. Consider, as an example, oxidation of a methylpyridine to produce 1 kg of the pyr-idinecarboxylic acid this process would consume about 3 worth of potassium permanganate at 100% efficiency and would produce 0.7 kg of byproduct Mn02 for disposal or recycle. The same anodic reaction would consume only 0.30 of electrical power (for oxidation) and would not produce a significant amount of material for disposal. 

Very little work has been done on selectivity in anodic reactions of pyridines. Selective methoxylation and acetoxylation are known for al-kylbenzenes, but such reactions have not been reported for alkylpyridines. Also, reports on the oxidation of pyridines having aldehyde, ketone, halogen, hydroxyalkyl, or aminoalkyl functionalities are sparse. 

Because the merits of anodic reactions of pyridines have yet to be fully realized, the discussion will include reactions that have low reported yields but are nevertheless of industrial interest. This will be especially important for the... 

The potential-limiting anodic reaction in pyridine with perchlorate as supporting electrolyte is presumably the oxidation of pyridine to an onium ion, which with excess of pyridine forms A -(2-pyridyl)pyridinium perchlorate [228]. 

Cyclic voltammograms of 48 recorded in ACN solutions containing as much as fivefold excess of pyridine are almost identical to those obtained without this base89. In both cases the product of the anodic reaction is the dimer 49. Identical electrochemical responses in the presence and in the absence of pyridine imply that there are no detectable interactions between the cation radical 48 and the pyridine molecules. However, diverse transformation of the decay profiles of 48 depending on the concentration of pyridine was observed using an electron transfer stopped-flow technique. The last observation was ascribed to the interaction between 48+ and pyridine, in which the proton is extracted by the molecule of the base89. One can therefore assume that this is an example of the process for which the voltammetric measurements at conventional scan rates cannot give full information about the pathway of the electrochemical reaction. 

Diphenylanthracene (DPA) has also been an important substrate in pyridination reactions. Anodic reaction leads to a di-pyridinium ion [32]. Marcoux (1971) found from the use of working curves that although the pyridination data could be described by both ECE and disproportionation processes, the data fitted disproportionation better. In contrast, Blount (1973), with transparent electrodes, and Svanholm and Parker (1973), with rotating disk electrodes, find that pyridination of DPA is an ECE reaction, following the pattern of Sioda s (1968) hydroxylation reaction. Anodic oxidation of DPA in the presence of 2,5-, 2,6-, and 3,5-... 

The corrosion of tin by nitric acid and its inhibition by n-alkylamines has been reportedThe action of perchloric acid on tin has been studied " and sulphuric acid corrosion inhibition by aniline, pyridine and their derivatives as well as sulphones, sulphoxides and sulphides described. Attack of tin by oxalic, citric and tartaric acids was found to be under the anodic control of the Sn salts in solution in oxygen free conditions . In a study of tin contaminated by up to 1200 ppm Sb, it was demonstrated that the modified surface chemistry catalysed the hydrogen evolution reaction in deaerated citric acid solution. 

The Karl Fischer procedure has now been simplified and the accuracy improved by modification to a coulometric method (Chapter 14). In this procedure the sample under test is added to a pyridine-methanol solution containing sulphur dioxide and a soluble iodide. Upon electrolysis, iodine is liberated at the anode and reactions (a) and (b) then follow the end point is detected by a pair of electrodes which function as a biamperometric detection system and indicate the presence of free iodine. Since one mole of iodine reacts with one mole of water it follows that 1 mg of water is equivalent to 10.71 coulombs. 

Foreign cations can increasingly lower the yield in the order Fe, Co " < Ca " < Mn < Pb " [22]. This is possibly due to the formation of oxide layers at the anode [42], Alkali and alkaline earth metal ions, alkylammonium ions and also zinc or nickel cations do not effect the Kolbe reaction [40] and are therefore the counterions of choice in preparative applications. Methanol is the best suited solvent for Kolbe electrolysis [7, 43]. Its oxidation is extensively inhibited by the formation of the carboxylate layer. The following electrolytes with methanol as solvent have been used MeOH-sodium carboxylate [44], MeOH—MeONa [45, 46], MeOH—NaOH [47], MeOH—EtsN-pyridine [48]. The yield of the Kolbe dimer decreases in media that contain more than 4% water. 

Dihydropyridines and their /V-alkyl derivatives undergo anodic oxidation in basic medium to the corresponding pyridines (reaction 27). The process may be complicated by the presence of other moieties for example, a nitro group may reductively condense... 

Cobaloxime(I), electrochemically regenerated from chloro(pyridine)-cobaloxime (III) (232), has been employed as a mediator in the reductive cleavage of the C—Br bond of 2-bromoalkyl 2-alkynyl ethers (253), giving (254) through radical trapping ofthe internal olefin (Scheme 95) [390]. An interesting feature of the radical cyclization (253) (254) is the reaction in methanol, unlike the trialkyltin hydride-promoted radical reactions that need an aprotic nonpolar solvent. An improved procedure for the electroreductive radical cyclization of (253) has been attained by the combined use of cobaloxime(III) (232) and a zinc plate as a sacrificial anode in an undivided cell [391]. The procedure is advantageous in terms of the turnover of the catalyst and the convenience of the operation. 

In 1981 we published the first paper [22] on the synthesis of s-triazolo[4,3-a]pyridinium salts, 4, by the anodic oxidation of hydrazones 3 in the presence of pyridine (Scheme 5). In our working mechanistic scheme we proposed nitrilimine as the possible intermediate and pointed out that this reaction opens the door to a wide range of heterocyclic systems via anodic oxidation of aldehyde hydrazones through 1,3-dipolar cycloaddition reactions of the nitrilimine involved. 

Oxidation in the presence of pyridine gave the products in 60-85% yield, whereas the electrolysis without pyridine lowered the yield to 10-20% and the products of hydrolysis, because of the accumulation of the acid in the anodic compartment, were identified. The reaction mechanism was proposed on the basis of LSV and CPSV results. The values of dEp/dlogv = 30 mV and dEp/dlogC = 0 mV point to the occurrence of a first-order rate-determining step. Comparison of the CPSV slope values of 58 mV with the theoretical value... 

We found that conventional electrolysis (of the partially-neutralised salt) in methanol produced a very rapid increase in applied cell-voltage and the attainment of no effective product (Column I). This was due to the production of a pale coloured coating at the anode which caused the reaction to cease. This is a well known occurrence in electro-organic chemistry [61] and the remedy is to add pyridine to keep the electrode dean, presumably by solubilising the inhibiting layer. Column II shows the product ratios from the silent reaction in the presence of 13 % (v/v) of pyridine. Here there is 60 % of... 

Oxidation of acridine in anhydrous acetonitrile leads to a dimer 65 formed by reaction of the nitrogen in one molecule of the substrate with the point of highest positive charge density in a radical-cation [208]. Anodic oxidation of neat pyridine... 

Oxidation of methylpyridines in 60-80 % sulphuric acid at a lead dioxide anode leads to the pyridinecarboxylic acid [213]. The sulphuric acid concentration is critical and little of the product is formed in dilute sulphuric acid [214]. In these reactions, electron loss from the n-system is driven by concerted cleavage of a carbon-hydrogen bond in the methyl substituent. This leaves a pyridylmethyl radical, which is then further oxidised to the acid, fhe procedure is run on a technical scale in a divided cell to give the pyridinecarboxylic acid in 80 % yields [215]. Oxida-tionof quinoline under the same conditions leads to pyridine-2,3-dicarboxylic acid [214, 216]. 3-HaIoquino ines afford the 5-halopyridine-2,3-dicarboxylic acid [217]. Quinoxaline is converted to pyrazine-2,3-dicarboxylic acid by oxidation at a copper anode in aqueous sodium hydroxide containing potassium permanganate [218]. 

I. 4-methoxyacetophenone (30 //moles) was added as an internal standard. The reaction was stopped after 2 hours by partitioning the mixture between methylene chloride and saturated sodium bicarbonate solution. The aqueous layer was twice extracted with methylene chloride and the extracts combined. The products were analyzed by GC after acetylation with excess 1 1 acetic anhydride/pyridine for 24 hours at room temperature. The oxidations of anisyl alcohol, in the presence of veratryl alcohol or 1,4-dimethoxybenzene, were performed as indicated in Table III and IV in 6 ml of phosphate buffer (pH 3.0). Other conditions were the same as for the oxidation of veratryl alcohol described above. TDCSPPFeCl remaining after the reaction was estimated from its Soret band absorption before and after the reaction. For the decolorization of Poly B-411 (IV) by TDCSPPFeCl and mCPBA, 25 //moles of mCPBA were added to 25 ml 0.05% Poly B-411 containing 0.01 //moles TDCSPPFeCl, 25 //moles of manganese sulfate and 1.5 mmoles of lactic acid buffered at pH 4.5. The decolorization of Poly B-411 was followed by the decrease in absorption at 596 nm. For the electrochemical decolorization of Poly B-411 in the presence of veratryl alcohol, a two-compartment cell was used. A glassy carbon plate was used as the anode, a platinum plate as the auxiliary electrode, and a silver wire as the reference electrode. The potential was controlled at 0.900 V. Poly B-411 (50 ml, 0.005%) in pH 3 buffer was added to the anode compartment and pH 3 buffer was added to the cathode compartment to the same level. The decolorization of Poly B-411 was followed by the change in absorbance at 596 nm and the simultaneous oxidation of veratryl alcohol was followed at 310 nm. The same electrochemical apparatus was used for the decolorization of Poly B-411 adsorbed onto filter paper. Tetrabutylammonium perchlorate (TBAP) was used as supporting electrolyte when methylene chloride was the solvent. 

The formation of arylzinc reagents can also be accomplished by using electrochemical methods. With a sacrificial zinc anode and in the presence of nickel 2,2-bipyridyl, polyfunctional zinc reagents of type 36 can be prepared in excellent yields (Scheme 14) . An electrochemical conversion of aryl halides to arylzinc compounds can also be achieved by a cobalt catalysis in DMF/pyridine mixture . The mechanism of this reaction has been carefully studied . This method can also be applied to heterocyclic compounds such as 2- or 3-chloropyridine and 2- or 3-bromothiophenes . Zinc can also be elec-trochemically activated and a mixture of zinc metal and small amounts of zinc formed by electroreduction of zinc halides are very reactive toward a-bromoesters and allylic or benzylic bromides . ... 

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 primarily formed radical-cation dimerizes at C-3 to bis(l-phenyl-A2-pyrazolin-3-yl) if C-3 is unsubstituted.281 By-products include biphenyl derivatives formed by an alternative dimerization of the parent radical-cation. The major product is further oxidized under the reaction conditions to stable cations. By blocking the para position of the phenyl ring in the 1-position, a persistent radical would be expected, and in the presence of a base, e.g., pyridine, the corresponding pyrazole was obtained.284,285 The anodic oxidation of 1,5-diphenyl-3-(4-hydroxycoumarinyl)-A2-pyrazoline in CH3CN-Et4NC104 solution, containing pyridine, resulted in the isolation of l,5-diphenyl-3-(4-hydroxycoumarinyl)pyrazole in 95% yield when the para position was not blocked.290... 

An unusual type of reaction is anodic reduction which can be performed at certain metal anodes. Thus, when magnesium is used as an anode in the electrolysis of benzophenone in pyridine/sodium iodide solution, the anode is consumed and benzopinacol can be isolated from the anolyte 15S). Here reduction by univalent magnesium ion is postulated ... 

Anodic treatment of 3,5-lutidine (35) on BDD electrodes also turned out to be challenging. Only traces of the desired pyridine-3,5-dicarboxylic acid (36) could be detected. As electrolyte a dilute NaOH solution was employed. The mineralization and decomposition seem to be the dominant reaction pathways (Scheme 16). 

The characteristics of the electrooxidation of fluorosulfate anions in the electrolysis of a potassium fluorosulfate solution in fluorosulfonic acid have been investigated. The formation of oxide layers on platinum and the modification of glassy carbon with fluorosulfate groups during anodic polarization in fluorosulfonic acid are studied. The reactions of fiuoroolefin fluorosulfation are considered and a mechanism is suggested223. Trifluoromethylation of carbonyl compounds can be achieved using bromo-trifluoromethane and a sacrificial electrode in solvents such as DMF/pyridine, and DMF/TMEDA, as seen in equation 126224. 

Marcoux and Adams have carried out a study of the anodic oxidation of a range of azines in acetonitrile at a platinum electrode.347 With the exception of pyridine which could not be oxidized under these conditions, all the other azines were oxidized in a complicated process in which one electron per molecule was transferred to the electrode. The reaction was investigated in some detail for acridine, and the main product was found to be an acridyl-acridinium perchlorate (perchlorate being supplied by the supporting electrolyte). This result, which is directly comparable with that for pyridine oxidation by peroxydisulfate is persuasive evidence for the mediation of the... 

A wide variety of compounds have been selectively monofluorinated in the benzylic position by anodic oxidation in 70% hydrogen fluoridc/pyridine, tricthylamine trishydrofiuoride in sulfolane, triethylamine trishydrofluoride, and triethylaminc trishydrofluoride in acetonitrile. I n general the reaction supports a wide range of substrates with benzyl fluorides formed selectively and in high yield. 

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