Oxidations, indirect electrochemical synthesis

Electrochemical oxidations and reductions provide environmentally safe methods for casing out organic synthesis. Anodic oxidation is the optimal technique for some oxidations, such as the Kolbe oxidation of carboxylic acids. However, many oxidations that can be carried out in high yield with the appropriate chemical oxidant cannot be accomplished by anodic oxidation. Indirect electrochemical oxidation provides a potential solution to this problem (50, 51). The reagent (mediator) carries out the oxidation of the substrate giving the product selectively and the reduced form of the mediator. The reduced form of the mediator is then oxidized electrochemically to generate the useful oxidized form of the mediator. The mediator is therefore used only in catalytic amounts. Indirect electrochemical oxidations and reductions thus have the potential to achieve the selectivity of chemical reactions with the environmental benefits of electrochemical methods. 

Other mediators which have been used in combination with diaphorase for the regeneration of NAD+ are riboflavin and Vitamin K3, which is 2,3-dimethyl-1,4-naphthoquinone. However, especially riboflavin is not stable enough for synthetic applications [40]. Better stability is exhibited by phenanthrolindiones as mediators. In combination with diaphorase, Ohshiro [41] showed the indirect electrochemical oxidation of cyclohexanol to cyclohexanone using the NAD+ dependent HLADH with a turnover frequency of two per hour. For an effective enzymatic synthesis, this turnover frequency, however, would be too small. In our own studies, we were able to accelerate the NAD(P)+ regeneration considerably by lowering the electron density within the... 

In addition to the synthesis of saccharin, also a number of other side-chain oxidations have been studied leading to aromatic carboxylic acids by indirect electrochemical oxidation using chromic acid as oxidizing agent. They include the oxidation of p-nitrotoluene 2,4-dinitrotoluene toluene, p-xylene, and p-tolualdehyde... 

The indirect electrochemical generation of propylene oxide via propylene chloro- or bromohydrin using anodically generated hypochlorite or hypobromite has been studied very intensively. The reason is the lack of a technically useful process for the synthesis of propylene oxide by way of heterogeneous catalysis. The propylene halohydrins are saponified using the cathodically generated sodium hydroxide (Eqs. (42)-(47)) (Table 4. No. 12-15)... 

A phosgene-free synthesis of alkylisocyanates makes use of the indirect electrochemical oxidation in the alpha-position to nitrogen of formamides. Bromide in methanol solution acts as the redox catalyst, which, presumably, is oxidized to the methyl hypobromite [9] ... 

Covalent fluorination of graphite is a common side reaction to the electrochemical formation of neutral graphite salts of such complex fluoride ions as [PFg] . An indirect RT synthesis of graphite fluoride is by anodic oxidation of graphite in nonaqueous solutions of F plus [BF4] salts C BF, which is formed in the primary step, is converted to graphite fluoride by an exchange process. 

Side chain oxidation of aromatics by Mn(III)-mediated indirect electrochemical oxidation is well known (50, 51, 85). Several groups have recently examined Mn(OAc)3-mediated electrochemical oxidations. Coleman et. al, at Monsanto have developed a procedure for the synthesis of sorbic acid precursors from acetic acid and butadiene using electrochemical mediated Mn(OAc)3 oxidation at 100 °C in acetic acid under pressure with graphite plates or a graphite felt anode (91). These authors concluded that this approach was practical for the large scale synthesis of sorbic acid. 

Within a potential range where radicals (like CF ) are not readily reduced or/and using indirect formation in solution by means of electron carrier, a chemistry—rather similar to that already developed by the Kolbe method by oxidation of CF3COO at a platninum anode—can be developed. Thus, Medebielle [193] showed that radical additional onto electron-rich olefins was possible and applied this for convenient synthesis of fluorinated heterocyclic compounds. Let us stress that the electrochemical process is in this case stoichiometric in electrons. 

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