title: ONSH: optimization of oxidative alkylamination reactions through study of the reaction mechanism.
abstract: Oxidative alkylamination of electron-deficient (hetero)aromatic compounds, via the nucleophilic substitution of hydrogen, is a methodology that has made significant progress since the introduction of AgPy(2)MnO(4) as oxidant. This oxidant generally gives good conversions and yields, whereas the use of KMnO(4) only sometimes works equally well. In order to rationalize this, the reaction mechanism of oxidative alkylamination has been studied. 3-Nitropyridine (1), 1,3-dinitrobenzene (2), and quinazoline (3) were chosen as model substrates and n-butylamine and pyrrolidine as model alkylamines. The rate-limiting step of the mechanism for these substrate/alkylamine combinations was determined. With the use of (1)H NMR spectroscopy thermodynamic properties of sigma(Eta)-adduct formation were deduced and the effect of additives on the adduct formation was investigated. The fundamental insights resulting from these studies led to the identification of a cheap additive (tetrabutylammonium chloride), which in combination with the standard and cheap oxidant KMnO(4) generally gave excellent yields, similar to the ones previously obtained with more expensive AgPy(2)MnO(4).
authors.affiliation: Department of Chemistry, Organic Synthesis, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Verbeeck
authors.forename: Wouter A
authors.initials: WA
authors.lastname: Herrebout
authors.forename: Anna V
authors.initials: AV
authors.lastname: Gulevskaya
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: van der Veken
authors.forename: Bert U W
authors.initials: BU
authors.lastname: Maes
mesh_terms: D000586:Amination; D000588:Amines / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction; D013057:Spectrum Analysis; D013816:Thermodynamics
chemical_list: D000588:Amines