Carboxylic acids Kolbe electrolysis

Anodic Decarboxylation of Carboxylic Acids (Kolbe Electrolysis)... 

One typical radical reaction is a coupling reaction. Oxidative decarboxylation coupling reaction of carboxylic acids by electrolysis (Kolbe electrolysis), intramolecular coupling reaction of diesters with Na (acyloin condensation), formation of pinacols from ketones or aldehydes with Na or Mg are well known classical methods [1,2]. Recently, oxidative... 

Kolbe reaction The pre >aration of saturated or unsaturated hydrocarbons by the electrolysis of solutions of the alkali salts of aliphatic carboxylic acids. Thus, ethanoic acid gives ethane,... 

Electrolysis of carboxylic acid salts m solution causes decaboxyladve coupling similar to Kolbe reaction. Thus, eleclrolysis of 3,3,3-trifluoro-2-trifluoromethyl-propanoic acid in die presence of some of its potassium salt gives the corresponding fluoroalkane in a satisfactory yield [7d] (equation 67). 

Kolbe electrolysis is a powerful method of generating radicals for synthetic applications. These radicals can combine to symmetrical dimers (chap 4), to unsymmetrical coupling products (chap 5), or can be added to double bonds (chap 6) (Eq. 1, path a). The reaction is performed in the laboratory and in the technical scale. Depending on the reaction conditions (electrode material, pH of the electrolyte, current density, additives) and structural parameters of the carboxylates, the intermediate radical can be further oxidized to a carbocation (Eq. 1, path b). The cation can rearrange, undergo fragmentation and subsequently solvolyse or eliminate to products. This path is frequently called non-Kolbe electrolysis. In this way radical and carbenium-ion derived products can be obtained from a wide variety of carboxylic acids. 

Faraday, in 1834, was the first to encounter Kolbe-electrolysis, when he studied the electrolysis of an aqueous acetate solution [1], However, it was Kolbe, in 1849, who recognized the reaction and applied it to the synthesis of a number of hydrocarbons [2]. Thereby the name of the reaction originated. Later on Wurtz demonstrated that unsymmetrical coupling products could be prepared by coelectrolysis of two different alkanoates [3]. Difficulties in the coupling of dicarboxylic acids were overcome by Crum-Brown and Walker, when they electrolysed the half esters of the diacids instead [4]. This way a simple route to useful long chain l,n-dicarboxylic acids was developed. In some cases the Kolbe dimerization failed and alkenes, alcohols or esters became the main products. The formation of alcohols by anodic oxidation of carboxylates in water was called the Hofer-Moest reaction [5]. Further applications and limitations were afterwards foimd by Fichter [6]. Weedon extensively applied the Kolbe reaction to the synthesis of rare fatty acids and similar natural products [7]. Later on key features of the mechanism were worked out by Eberson [8] and Utley [9] from the point of view of organic chemists and by Conway [10] from the point of view of a physical chemist. In Germany [11], Russia [12], and Japan [13] Kolbe electrolysis of adipic halfesters has been scaled up to a technical process. 

The nature of the cathode material is not critical in the Kolbe reaction. The reduction of protons from the carboxylic acid is the main process, so that the electrolysis can normally be conducted in an undivided cell. For substrates with double or triple bonds, however, a platinum cathode should be avoided, as cathodic hydrogenation can occur there. A steel cathode should be used, instead. 

The coupling of carboxylic acids has been profitably used in natural product synthesis. Kolbe electrolysis of 10 is part of a (+) x-onocerin synthesis [120], the dimerization of il leads to a pentacyclosqualene [121], the electrolysis of 12 afforded a dime-with two quaternary carbon atoms [122], and 2,6,10,15,19,23-hexamethyltetracontane has been synthesized from 13 [123]. 

Despite of the disadvantage, that at least one symmetrical dimer is formed as a major side product, mixed Kolbe electrolysis has turned out to be a powerful synthetic method. It enables the efficient synthesis of rare fatty acids, pheromones, chiral building blocks or non proteinogenic amino acids. The starting compounds are either accessible from the large pool of fatty acids or can be easily prepared via the potent methodologies for the construction of carboxylic acids. 

Another advantage of the synthesis by mixed Kolbe electrolysis is that polar groups in the carboxylic acid are tolerated in radical coupling. This makes additional protection-deprotection steps unneccessary, which are often needed in polar CC-bond forming reactions and can make these approaches less attractive in such cases. 

Table 6. Cross-coupling by Kolbe electrolysis of unsubstituted (A) with substituted carboxylic acids (B)...

Non-Kolbe Electrolysis of Carboxylic Acids to Ethers, Esters, and Alcohols... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Non-Kolbe electrolysis of carboxylic acids in acetonitrile/water leads to acetamides as main products [294] (Table 10). The mechanism has been investigated by using " C-labeled carboxylic acids. The results are rationalized by assuming a reaction layer rich of carboxylate resulting in the formation of a diacylamide that is hydrolyzed... 

The carbocations generated by non-Kolbe electrolysis can rearrange by alkyl, phenyl or oxygen migration. The migratory aptitudes of different alkyl groups have been studied in the rearrangement of a-hydroxy carboxylic acids (Eq. 34) [323]. 

Non-Kolbe electrolysis of alicyclic p-hydroxy carboxylic acids offers interesting applications for the one-carbon ring extension of cyclic ketones (Eq. 35) [242c]. The starting compounds are easily available by Reformatsky reaction with cyclic ketones. Some examples are summarized in Table 13. Dimethylformamide as solvent and graphite as anode material appear to be optimal for this reaction. 

Non-Kolbe electrolysis of carboxylic acids can be directed towards a selective fragmentation, when the initially formed carbocation is better stabilized in the y-position by a hydroxy or trimethylsilyl group. In this way the reaction can be used for a three-carbon (Eq. 36) [335] (Table 14, No. 1) or four-carbon ring extension (Eq. 37) [27] (Table 14, Nos. 2-4). Furthermore it can be employed for the stereo-... 

Pseudo-Kolbe electrolysis is the name given to anodic decarboxylations where the electron transfer does not occur from the carboxylate but from a group attached to it [31]. These oxidations are characterized by potentials that are much lower than the critical potential for the Kolbe electrolysis. The salt of p-methoxyphenylacetic acid can be oxidized in methanol to afford the corresponding methyl ether as the sole product. The low oxidation potential of 1.4 V (see) suggests, that the electron is being transferred from the aromatic nucleus (Eq. 39) [31]. 

Recent Contributions of Kolbe Electrolysis to Organic Synthesis Table 14. Fragmentation of carboxylic acids by non-Kolbe electrolysis... 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

Allyl radicals can, of course, also be generated by electrolysis of the corresponding /J,y-unsaturated carboxylic acids together with a second carboxylic acid. This mixed Kolbe electrolysis method has been used to study the recombination of allyl radical 32 with the undecyl radical 3370. Recombination leads to the formation of adducts 34 and 35 in a ratio of 72 28, again preferring the product with the higher substituted double bond (equation 16). 

Kolbe electrolysis of trilfuoromethylated carboxylic acids has been shown to be a versatile method for providing useful building blocks having a CF3 group. Seebach and Renaud have prepared new types of trifluoromethylated chiral building blocks from enantiomerically pure 3-hydroxy-4,4,4-trifluorobutyric acid (Scheme 7.6) [76]. 

While anodic amide oxidations have found the most synthetic use to date, the oxidation of nitrogen-containing molecules is not limited to amide substrates. A variety of amine oxidations have been studied, and the Kolbe electrolysis of carboxylic acids has been used to generate nitrogen-based reactive intermediates. Many of these reactions also offer unique synthetic advantages (Sects. 10.2 and 10.3). 

One of the best-known anodic oxidation reactions is still the Kolbe electrolysis [38]. These reactions typically involve the decarboxylation of a carboxylic acid and... 

Cations resulting from a two-electron oxidation of carboxylic acids (non-Kolbe electrolysis) or from compounds having protons in the a-position to heteroatoms as shown in Scheme 3 [6] react with nucleophilic centers. In the last case. 

The Kolbe electrolysis has been used by Schafer and coworkers to synthetize substituted furans or pyrrolidines in good yields by a carbon-carbon coupling reaction after co-oxidations of 6-alkenoic acids and various carboxylic acids [4, 5, 20, 21] (Schemes 2 and 15). In Scheme 15, the... 

Kolbe hydrocarbon synthesis orgchem The production of an alkane by the electrolysis of a water-soluble salt of a carboxylic acid. kol-bo. hT-dro kar-bon, sin-th3-s3s Kolbe-Schmitt synthesis org chem The reaction of carbon dioxide with sodium phenoxide at 125°C to give salicyclic acid. kol-bo shmit, sin-th3-s3s Konowaioff ruie phys chem An empirical rule which states that in the vapor over a liquid mixture there is a higher proportion of that component which, when added to the liquid, raises its vapor pressure, than of other components., k6-n9 va-lof, rul ... 

Diacyl peroxides (16, R2 = R1 = alkyl or aryl) have been obtained from the oxidation of carboxylic acid potassium salts by Kolbe electrolysis or by elemental fluorine. 

In the so-called non-Kolbe electrolysis, the carboxylate group is substituted by a nucleophile like methanol. This is especially effective if heteroatoms like nitrogen or oxygen are situated in the a-position. A number of amino acid derivatives have thus been transformed into the already mentioned N, (9-acetals as effective amidoalkylation reagents [28] ... 

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