One-pot oxidative N-demethylation of tropane alkaloids with hydrogen peroxide and a Fe-III-TAML catalyst

The oxidative N-demethylation of tropane alkaloids to their nortropane derivatives has been investigated using H2O2 and an iron(III) tetraamido macrocycle (Fe-III-TAML) catalyst. The yields of the nortropanes were found to be dependent on the amount of H2O2 used in the reaction, the catalyst loading, the nature of the organic co-solvent and the type of tropine substrate. N-Hydroxy-nortropane, N-formyl-nortropane and tropane-N-oxide derivatives were identified as by-products of the reaction. After screening various reaction conditions, the optimised conditions were applied to the N-demethylation of atropine and scopolamine at preparative scales and the desired products, noratropine and norscopolamine, obtained following one pot reactions in good yields and high purity without the need for any chromatographic purification steps.