Abstract

Aromatic compounds containing a redox-active hydroxylamine functionality are of great importance in biology and in synthetic organic chemistry. For example, arylhydroxylamines can act as a nitric oxide donor in mammals under certain conditions. They also participate as substrates in organic reactions for C–N bond formation, e.g. the metal-catalyzed nitroso-ene reaction. The redox conversions of arylhydroxylamines are, however, not well studied because of the high reactivity of these compounds and the ensuing formation of undesired side products. To address this challenge and gain insight into the redox behaviour of arylhydroxylamines in a systematic manner, we designed a family of ligands that possess an arylhydroxylamine function and can accommodate a variety of metal ions. This thesis reports the synthesis of these ligands, their complexation with three metal ions and the capacity of the complexes to catalyze a test organic reaction, the aerobic oxidation of alcohols into aldehydes.
Ligand design is based on the well-known family of salen ligands. We installed a pendant nitro group (ArNO2) on one side of the ligand via a sulphonamide linkage, while substitutions on the salicylimine side afford structural and electronic variety. Partial reduction of the nitro group provides access to the corresponding arylhydroxylamine (ArNHOH) ligand, but the reduction conditions have to be fine-tuned to avoid over-reduction to the amine (ArNH2) function. This was achieved either by catalytic hydrogenation over a poisoned palladium/charcoal catalyst or by stoichiometric transfer hydrogenation with zinc and ammonium formate. After optimization, these methods yielded four NHOH-containing ligands.
Subsequent complexation of the ligands with copper(II), nickel(II) and zinc(II) did not trigger a reaction with the redox-active NHOH function, contrary to the common belief that hydroxylamines disproportionate in the presence of metal ions. These unique complexes have been characterized by single-crystal X-ray diffraction, 1H-NMR, and mass spectrometry. These studies reveal that the hydroxylamine function is engaged in an intramolecular hydrogen bond, which we hypothesized is responsible for the metastability of the NHOH function.
The complexes were screened as pre-catalysts for the aerobic oxidation of primary and benzylic alcohols to produce aldehydes. Only with benzylic alcohols was significant turnover observed, and only with the copper complexes (copper is known to enable oxygen-activation turnover). More importantly, control experiments reveal that the NHOH function is crucial for catalysis, which portends a similar mechanism as in the Markó alcohol oxidation system.
Further studies will focus on characterizing the fate of the NO bond during turnover, with the prospect of designing a novel family of catalysts for two-electron oxidation reactions.