Mechanism of the oxidation of yohimbine and two of its 7H-substituted derivatives by sodium peroxodisulfate

Abstract

The mechanism of the oxidation of a Rauwolfia alkaloid, yohimbine, Y, by sodium peroxodisulfate, PDS, has been investigated in 40% v/v methanol–water at different PDS and acid concentrations. Because 3H-indoles have been reported as intermediates in the oxidation of this alkaloid, we have also analyzed the reactivity of 7-acetoxy- and 7-methoxy-7H-yohimbine, AcOY and MeOY, respectively. From these studies, we conclude that in the oxidation of Y with PDS, the first step of the reaction is an electrophilic attack of PDS at the C-7 atom of the substrate, to form the corresponding 3H-indole intermediate. This step is always the same, independent of the range of sulfuric acid concentration. Once the 3H-indole intermediate is formed, an imonium–enamonium equilibrium is established, the reactivity of the tautomeric forms and, therefore, the reaction products being strongly dependent on the media. That is, competing parallel reactions occur. In high sulfuric acid and low PDS concentrations, a rearrangement step, from the enamonium tautomer, produces the dehydroderivative, DH. At low acidities and high PDS concentrations, a new electrophilic PDS attack at the enamonium tautomer gives rise to the dioxy derivative, Dx. Under intermediate concentrations of PDS and acid where both steps compete, both reaction products are obtained. A global mechanism is postulated to account for the experimental rate equations.