Synthesis of dehydrocholic acid by electrochemical oxidation of cholic acid

The synthesis of dehydrocholic acid (3,7,12-trichetocholan-24-oic acid) is generally carried out by chemical oxidation of cholic acid (3,7,12-trihydroxycholan-24-oic acid), with liquid Bromine and other reactants commonly used in oxidative synthesis processes. However, although convenient because of their low cost, their use involves drawbacks like the environmental impact and formation of undesired by-products, like brominated or chlorinated derivatives. In this light, it has been thought of interest to try the preparation of dehydrocholic acid by anodic oxidation of cholic acid. Experiments have been carried out in alkaline aqueous media and in aquo-organic media (water-dimethylether of ethylene glycol). In the latter case the v/v ratio between the organic solvent and water was 2:1. Sodium perchlorate has been used as supporting electrolyte. Experiments have been carried out without and with mediation by active chlorine, using sodium chloride as mediation precursor. The oxidative process has been studied at Ti/PbO2, Ti/Pt and graphite anodes . At Ti/PbO2 electrodes the direct electrochemical oxidation of cholic acid does not occur, both in aqueous and aquo-organic media. The conversion could be achieved only through chloride mediation. The optimal NaCl concentration was about 14.0 g dm-3. Higher concentrations caused a decrease of the faradaic yield of the oxidation process. Temperature and current density also play an important role. Decrease of the faradaic yield was observed with increasing the electrolysis temperature. Three current densities j, were tested: 31.25, 62.5, 125 A m-2. The highest faradaic yields (33%) was obtained at the lowest j value. Apparently the increase of temperature or of current density favour the competitive oxygen evolution reaction. The first intermediate detected was the 7-cheto derivative. At longer electrolysis times a small amount of the 12-cheto derivative was also detected, together with larger amounts of the 7,12 dicheto acid and of the final product itself. Significant amount of the latter could be found only when most of cholic acid was already converted into the monocheto- and dicheto- forms. No chlorine was detected in the evolved gases during the electrolyses carried out under the above conditions and no hypochlorite and chlorate were found at the end of the oxidation of the organic substrate. The increase of the reactant concentration from 8.3 to 16.6 g dm-3, caused a quite significant decrease in the faradaic yield of the dehydrocholic acid formation. In this case most of the products at the 14th hour of electrolysis were the 7-cheto- and the 7,12-dicheto form. Larger amount of the 12-cheto-form was also detected. Under analogous conditions the oxidation of cholic acid at Ti/Pt did not take place In aqueous media (pH 12) cholic acid is slowly converted to the 7-cheto metabolite. Results obtained at graphite electrodes are similar to those obtained at Ti/PbO2 electrodes. Under the same conditions of current density, sodium chloride concentration and cholic acid concentration, the faradaic yield for the conversion to dehydrocholic acid is slightly lower than at Ti/PbO2 electrodes. Chemical oxidation by sodium hypochlorite in the same solvent mixture did not lead to the dehydro derivative, indicating that in this case mediation by active chlorine is essentially based on surface species.