Non-Kolbe Reactions

The anodic oxidation of a-substituted carboxylic acids very frequently leads to the two-electron oxidation products instead of the one-electron products. The reaction was investigated in case of a number of amino acid derivatives by Tanabe 247 249 and others. 

The electrosynthesis of N,O-acetals was investigated by Hoechst 250). However, this route cannot compete with the anodic methoxylation of carboxamides. 

At Shell 25I), this reaction principle was applied to a novel isocyanate synthesis  

If methanol is used as solvent, the corresponding urethanes are formed (conversion 73% yield 69% current efficiency 45%). 

A laboratory synthesis for vanillin is based on this procedure. 2-Hydroxytetrahydro-furan, an intermediate for cytostatics, was produced from the corresponding carboxylic acid by electrochemical oxidation 253  

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Scheme 34 1,2-Rearrangement induced by the Non-Kolbe reaction as key step for a muscone synthesis.

Correspondingly, 4-acetoxy-2-azetidin-one (102) was prepared from 4-carboxy-2-azetidinone (101) by a non-Kolbe reaction (Eq. 13) [123],... 

On the other hand, in contrast with the non-Kolbe reaction of (113), that of L-serine derivative (115) gave an optically active a-methoxylated product (116) with 39% ee when graphite was used as the anode... 

The non-Kolbe reaction of trichloroacetic acid at platinum shows con etition with oxygen evolution. The formation of trichloromethy trichloroacetate only begins when the anode potential exceeds 2.35 V vs, see [63]. At lower anode potentials oxygen only is evolved. 

In many cases both Kolbe and non-Kolbe products are isolated from a reaction. Carboxylic acids with an a-alkyl substituent show a pronounced dual behaviour. In these cases, an increase in the acid concentration improves the yield of the Kolbe product. An example of the effect of increased substrate concentration is given in Kolbe s classical paper [47] where 2-methylbutyric acid in high concentration affords mostly a dimethylbexane whereas more recent workers [64], using more dilute solutions, obtained both this hydrocarbon and butan-2-ol. Some quantitative data is available (Table 9.2) for the products from oxidation of cyclohexanecar-boxylic acids to show the extent of Kolbe versus non-Kolbe reactions. The range of products is here increased through hydrogen atom abstraction by radical intermediates in the Kolbe reaction, which leads to some of the monomer hydrocarbon... 

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],... 

Substituents stabilising a carbonium ion influence the course of the anodic oxidation of carboxylic acids by promoting fast oxidation of the radical intermediate to the carbonium ion. Subsequent chemical steps are those expected of this ionic intermediate and the overall process is termed the non-Kolbe reaction. Reaction at... 

Non-Kolbe reactions are often favoured by skeletal reaiTangements which generate a more stable carbonium ion. Reaction of the cyclic ketal 22 is driven by formation of a carbonium ion stabilised by the oxygen substituent [114]. Reactions of nor-bomanecarboxylic acids are driven by the norbomane carbonium ion rearrangement [115, 116], Oxidation of adamant-1-ylacetic acid in methanol affords 1-methoxyhomoadamantane via a skeletal rearrangement [117],... 

The electrode material can also influence the product distribution, as shown in the Kolbe electrolysis of carboxylates. With platinum anodes, the Kolbe dimerization of the intermediate radicals predominates strongly (Eq. 22.5). At carbon anodes, however, further oxidation to the carbenium ion (non-Kolbe reaction or Hofer-Moest reaction) becomes the main pathway (Eq. 22.25). 

In the 1960s, a more promising expansion of the electrodecarboxylation reaction in terms of synthetic utility was recorded in which a carbenium intermediate R" " formed at the anode plays an important role [Eq. (7)] [4]. Depending on the structural characteristics of the carboxylates and/or electrochemical variables, the cation intermediate may undergo the so-called non-Kolbe reactions, for example, substitution, deprotonation, C-C bond cleavage, and rearrangement to provide alcohols, ethers, esters, amides, olefins, and others. 

Experimental variables affecting the course of the electrolytic decarboxylation of carboxylic acids are summarized in Table 2. For the Kolbe dimerization, the conditions specified for a one-electron process are recommended otherwise the reaction through carbenium ion (non-Kolbe reaction) may occur predominantly. It should be emphasized that even under the conditions most favorable for the Kolbe dimerization, the cation-derived products are usually formed to some extent or, in particular cases, as a major product, depending on the structure of the employed carboxylic acid. 

A -Acylated amino acids are anodically oxidized in methanol or acetic acid solution under decarboxylative methoxylation or acetoxylation via the intermediate A-acyliminium ion in the course of a Non-Kolbe reaction (Hofer-Moest reaction) according to Scheme 8, path b. This type of reaction has been used intensively for amidoalkylation reactions by Mori, Seebach, and Steckhan. These reactions were based on the results of Iwasaki applying N-acyl aminomalonic acid half esters [Eq. (46)] [239]. 

The use of other electrode materials (like graphite) allows the oxidation of the transient radical as a non-Kolbe reaction. The reaction turns out to be a two-electron process. The nature of products depends then on the nucleophilicity of the solvent. 

Geneste F, Cadoret M, Moinet C, Jezequel G (2002) Cyclic voltammetry and XPS analyses of graphite felt derivatized by non-Kolbe reactions in aqueous media. New J Chem 26 1261-1266... 

In oxidation, the anion associated with the PILs is oxidized. In the case of carboxyl-ates, the relatively low potential (1.5 V (vs. Ag/AgCl) mechanism proceeds according to the Kolbe reaction followed by the formation of dimers, whereas the oxidation of the alkyl radical at more anodic potential can be leading to products deriving from the carbocation, named the non-Kolbe reaction. The mechanism is described as follows ... 

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