Hofer-Moest reaction

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. 

A mixture of water/pyridine appears to be the solvent of choice to aid carbenium ion formation [246]. In the Hofer-Moest reaction the formation of alcohols is optimized by adding alkali bicarbonates, sulfates [39] or perchlorates. In methanol solution the presence of a small amount of sodium perchlorate shifts the decarboxylation totally to the carbenium ion pathway [31]. The structure of the carboxylate can also support non-Kolbe electrolysis. By comparing the products of the electrolysis of different carboxylates with the ionization potentials of the corresponding radicals one can draw the conclusion that alkyl radicals with gas phase ionization potentials smaller than 8 e V should be oxidized to carbenium ions [8 c] in the course of Kolbe electrolysis. This gives some indication in which cases preferential carbenium ion formation or radical dimerization is to be expected. Thus a-alkyl, cycloalkyl [, ... 

So the Kolbe syntheses may be named a noncatalyzed rather than an elec-trocatalyzed reaction and the Hofer-Moest reaction (41 g)—(41 h), although in most cases undesired, is heterogeneously catalyzed. 

A new stereoselective synthesis of 1,2,3-trisubstituted cyclopentanes based on the Wag-ner-Meerwein rearrangement of a 7-oxabicyclo[2.2.1]heptyl 2-cation starts with the Diels-Alder product of maleic anhydride and a furan (78TL2165, 79TL1691). The cycloadduct was hydrogenated and subjected to methanolysis. The half acid ester (47) was then electrolyzed at 0 °C to generate a cationic intermediate via the abnormal Kolbe reaction (Hofer-Moest reaction). Work-up under the usual conditions provided the 2-oxabicyclo[2.2.1]heptane (48) in 83% yield. Treatment of this compound in turn with perchloric acid effected hydrolysis of the ketal with formation of the trisubstituted cyclopentane (49) in nearly quantitative yield (Scheme 11). Cyclopentanes available from this route constitute useful... 

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). 

Where there is direct overlap with the valence band edge, the electron transfer process may be so facile as to give rise to the Hofer-Moest reaction (.2), in which the intermediate alkyl radical is itself oxidized (while it is still adsorbed to the electrode surface) to give a carbonium ion. The reaction of this carbonium ion with the aqueous electrolyte would then yield water-soluble products such as methanol, in keeping with our observation that anodic gas evolution is suppressed under these conditions. In acidic solutions, where the Kolbe reaction is energetically allowed, its kinetic competition with the other reactions on SrTiC>3 thus depends on the absence of defect surface states which are present in some electrode crystals and not in others. 

Hofer-Moest reaction. We do not attempt this discrimination as the electrochemical decarboxylation of carboxylates is always a blend of both pathways. 

If neutral salts are added to the electrolyte, especially if this consists of acetic acid only, with no acetate, the extent of the Kolbe reaction is diminished under these conditions also, methyl alcohol is formed by the so-called Hofer-Moest reaction (1902). When the conditions are such that the acetate is oxidized to ethane the anode potential is about 2.2... 

Electrocatalysis is manifested when it is found that the electrochemical rate constant, for an electrode process, standardized with respect to some reference potential (often the thermodynamic reversible potential for the same process) depends on the chemical nature of the electrode metal, the physical state of the electrode surface, the crystal orientation of single-crystal surfaces, or, for example, alloying effects. Also, the reaction mechanism and selectivity 4) may be found to be dependent on the above factors in special cases, for a given reactant, even the reaction pathway [4), for instance, in electrochemical reduction of ketones or alkyl halides, or electrochemical oxidation of aliphatic acids (the Kolbe and Hofer-Moest reactions), may depend on those factors. 

In the Kolbe reaction and in anodic carboxylation reactions, salts of carboxylic acids function as both substrate and electrolyte. Usually the presence of other anions diminishes the yield of the Kolbe reaction, whereas the presence of anions that are oxidizable with difficulty, like bicarbonate or perchlorate ions, favors the related Hofer-Moest reaction. 

The electrochemical hydroxylation and esterification in aqueous media, the so-called Hofer-Moest reaction, initially were regarded as a side reaction, but sometimes become the major reaction in the aqueous Kolbe reaction [5]. Such puzzling phenomena encountered in the early Kolbe reaction can be rationalized on the basis of the assumption just described above. 

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 conversion of carboxylic acids into alcohols with one less carbon atom is an important synthetic transformation. Such decarboxylative hydroxylations have proven to be difficult to accomplish by classical ionic methods. Electrochemical decarboxylation (Hofer-Moest reaction) [23] has been applied successfully to different types of carboxylic acids such as amino acids (Scheme 11, Eq. 11.1) [24]. This reaction proceeds through an intermediate radical that is further oxidized to a car-benium ion and trapped by the solvent. The efficiency of the second oxidation step (the formation of the carbenium ion) depends on the ionization potential of the in-... 

Other references related to the Hofer-Moest reaction are cited in the literature. ... 

This reaction is related to the Hofer-Moest Reaction. 

Kolbe and Hofer-Moest reactions Oxidation of amines Oxidation of amides Oxidation of alcohols and phenols Oxidation of ethers Oxidation of oximes, nitroalkanes, hydrazines Electrocoating... 

Several electrochemically important reactions occur on the surface of oxidized noble metal electrodes without reaction with the surface oxide. The oxide film then behaves as a new type of electrocatalyst surface on which the reaction proceeds, in distinction to the underlying metal. The oxide films are normally only one to three oxygen layers in thickness. The following inorganic reactions are of this class (a) O2 evolution, (b) CI2, (c) Br2 (to a small extent, since adsorbed Br blocks surface oxidation) and N2 evolution (from N3 ) while, in the case of organic reactions, (a) the Kolbe and Crum-Brown/Walker syntheses, as well as (b) the Hofer-Moest reaction, are of this type. ... 

By way of a further extension of this oxidation process, it was shown that, under specific conditions, the dimerization reaction could be suppressed, allowing formation of alcohols and esters—the so-called Hofer-Moest reaction ... 

The other anodic reactions of carboxylates, e.g., the Hofer-Moest reaction, are believed to involve carbonium ion intermediates. 

Following this were the investigations of Glasstone and Hick-ling, centered primarily on the Kolbe and Hofer-Moest reactions... 

The Hofer-Moest reaction, which is the formation of an alcohol rather than the hydrocarbon, was considered to occur whenever the conditions were not favorable for the Kolbe reaction ... 

Several variants have become established. The Hofer-Moest Reaction uses carbon rather than platinum anodes the intermediate radical loses another electron and becomes a carbocation which reacts with nucleophiles (Nu)" purposely added or adventitiously present (e.g., OH from water) ... 

Oxidative decarboxylation, as in the Kolbe reaction, is one of the oldest of all electrochemical oxidations. Whether such reactions parallel any reactions that occur in nature is still in question. Actually, the reaction can take two courses loss of an electron from a carboxylate and decarboxylation to form a radical which dimerizes or reacts with another radical, or loss of an electron followed by decarboxylation and loss of a second electron to form a carbocation (The Hofer-Moest reaction, 33). The carbocation may then be neutralized by reaction with nucleophile or another source of electrons. 

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