Oxidation of amides by laccase-generated aminoxyl radicals

The enzyme laccase from the fungus Trametes villosa catalyses the oxidation of two hydroxylamines (NOH), i.e., HPI (N-hydroxy-phthalimide) and HBT (1-hydroxy-benzotriazole), into their corresponding aminoxyl radicals (NO) PINO and BTNO. The ensuing oxidation of a few amides and lactames by PINO and BTNO has been investigated in buffered water solution (pH 5) at room temperature. The results from this chemo-enzymatic approach have been compared with a literature method that generates the aminoxyl radical PINO by the HPI/Co(II)/O2 chemical system, and uses it for the oxidation of similar amides. The merits of the aminoxyl radicals PINO and BTNO have been comparatively assessed in the chemo-enzymatic method, and the mechanism investigated. A Hammett treatment of the relative reactivity of oxidation of X-substituted-N-acetylbenzylamides in competition experiments supports a rate-determining H-abstraction route. With a few of the investigated substrates, stereoelectronic effects have been uncovered, and a rationalisation of their contribution to the reactivity of the H-abstraction route is offered, and supported by semiempirical calculations.