Surface-Mediated Reactions. 9. Selective Oxidation of Primary and Secondary Amines to Hydroxylamines¹

Abstract

OXONE over silica gel or, in some cases, alumina has been found to oxidize the primary and secondary amines 3 selectively to the corresponding hydroxylamines 4, in either the presence or absence of a solvent. Treatment of Boc-protected L-lysine (6) under the latter conditions afforded hydroxylamine 7 in excellent yield. The trialkylamine 1a and pyridine (1b), in which selectivity is not an issue, were readily oxidized to the corresponding oxides 2 by OXONE over silica gel or alumina, as well as by (CH(3))(3)COOH over silica gel. Solvent-free oxidation assisted by microwave irradiation was more forcing, while still affording the hydroxylamines 4 selectively, and is the synthetic method of choice. The mechanistic aspects of these reactions are discussed.

Synthesis of Hydroxylamines

“…Silicon-supported OXONE reagent oxidizes n-hexylamine into the corresponding hydroxylamine in good yield 285 .…”

Hydroxamic Acids: Chemistry, Bioactivity, and Solutionand Solid‐Phase Synthesis

“…In addition to the oxidation of amines with BPO [136,[138][139][140][141], there are four alternative routes for synthesizing hydroxylamines from amines as outlined in Scheme 3.21: (a) oxidation of primary and secondary amines using oxone over silica gel or, in certain instances, alumina [142], (b) oxidation of amines using dimethyldioxirane in acetone to give the acetonederived nitrone, followed by acid hydrolysis or hydroxylaminolysis [143], (c) selective mono-cyanomethylation of primary amines, followed by meta-chloroperoxybenzoic acid (m-CPBA) oxidation to give the nitrone and subsequent hydroxylaminolysis with hydroxylamine hydrochloride [144], and (d) reaction of an amine and an aromatic aldehyde to give an imine, followed by oxidation with m-CPBA to give the corresponding oxaziridine and hydrolysis to the hydroxylamine under acid-catalyzed conditions [145][146][147]. …”

Synthetic Applications of Oxone®

“…4 When Oxone ® is supported on silica or alumina, primary and secondary amines can also be oxidized selectively to hydroxylamines in either the presence or absence of a solvent. 5 …”

“…KHSO 4 . K 2 SO 4 ; its active component is potassium peroxymonosulfate (KHSO 5 ), a powerful oxidizing agent in synthetic organic chemistry which has proved to be a versatile reagent for various organic transformations. Oxone ® is commercially available and can be used immediately.…”