Indirect electrochemical synthesis

Fig. 4. Principle of an indirect electrochemical synthesis under application of chemically modified electrodes exemplified by a reduction...

Recent Advances in Indirect Electrochemical Synthesis. Indirect electrochemical synthesis has tremendous potential as an environmentally benign procedure since the selectivity of a chemical reaction can be obtained without the production of toxic or hazardous byproducts. Two recent reviews (50, 57) exhaustively cover the field through the mid 1980 s. Before describing our results, we will briefly survey recent advances in the field. 

Indirect electrochemical synthesis is an area of much current interest as indicated in the introduction to this chapter. This field has tremendous potential for carrying out reactions in high yield under reaction conditions that minimize the formation of polluting byproducts. 

Electroorganic Synthesis by Indirect Electrochemical Methods New Applications of Electrochemical Techniques ... 

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] ... 

Hildebrand F, Kohlmann C, Franz A, Liitz S (2008) Synthesis, characterization and application of new rhodium complexes for indirect electrochemical cofactor regeneration. Adv Synth Catal 350 909-918... 

Figure 26. Indirect electrochemical anaerobic reactivation of the enzyme GPO for the synthesis of dihydroxyacetone phosphate and its follow-up in situ coupling to the aldolase catalyzed formation of carbohydrates.

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. 

This is an example of an indirect electroorganic synthesis process with the aid of 06 ions as an electric charge carrier. The resulting Ce " ions must be electroche-mically regenerated in a seperate electrochemical reactor. 

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. 

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. 

We chose to study the generation of alkoxycarbenium ion 26 from thioacetal 28. The electrochemically generated ArS(ArSSAr)+, 37 which was well characterized by CSI-MS, was found to be quite effective for the generation of alkoxycarbenium ions, presumably because of its high thiophilicity (Scheme 17). The conversion of 28 to 26 requires 5 min at -78 °C. The alkoxycarbenium ion pool 26 thus obtained exhibited similar stability and reactivity to that obtained with the direct electrochemical method. The indirect cation pool method serves a powerful tool not only for mechanistic studies on highly reactive cations but also for rapid parallel synthesis. 

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