Studies of tertiary amine oxides. 11. Rearrangement of Acetylenic Amine Oxides

Abstract

Sixteen acetylenic amine oxides (5a–p) were prepared by the oxidation of the corresponding tertiary amines (4a–p) with m‐chloroperbenzoic acid. The N‐oxides are thermally unstable and undergo a rearrangement when stirred in an inert solvent yielding O‐allenyl hydroxylamines (6). The rearrangement proceeds by an intramolecular cyclic mechanism.

Novel Intramolecular Rearrangement of Tertiary PropargylamineN-Oxides

“…When we studied the chemical behavior of pargyline N -oxide ( 1 ) in protic media, we recognized novel type of a solvent-dependent rearrangement of tertiary propargylamine N -oxides. Pargyline N -oxide ( 1 ), a metabolite of the monoamine oxidase inhibitor pargyline, and similar tertiary propargylamine N -oxides − are known to undergo thermal Meisenheimer-type concerted [2,3] sigmatropic transformation in aprotic media (CH 2 Cl 2 , THF, and CCl 4 ), for example, to yield O -propadienyl hydroxylamine ( 2 ), which readily furnishes N -benzylidenemethylamine and propenal by a [1,5] hydrogen shift.…”

Medicinal Chemistry of Drugs with N-Oxide Functionalities

“…Peroxyacids are a particularly useful alternative to H 2 O 2 for the oxidation of tertiary amines, but their use is accompanied by a loss of functional group tolerance . While H 2 O 2 poorly reacts with double bonds, carbonyls, or thioethers in the absence of a catalyst, peroxyacids convert these functional groups to epoxides, esters, and sulfones, respectively. , The most commonly employed reagent on a laboratory scale is meta -chloroperbenzoic acid (mCPBA), and numerous synthetic procedures have been published (for an example, see Figure B). , However, mCPBA is disadvantageous for reactions on an industrial scale due to its high cost and safety concerns. A workaround is the in situ generation of peroxyacids by oxidizing the corresponding carboxylic acids with H 2 O 2 or other oxidants.…”

Novel 3-phenylprop-2-ynylamines as inhibitors of mammalian squalene epoxidaseElectronic supplementary information (ESI) available: Proton NMR spectra for the intermediate piperidines 56–60 and acetylenes 63-81 and 85,86. See http://www.rsc.org/suppdata/ob/b2/b209165h/

“…2 The cholesterol biosynthesis pathway can be interrupted at a number of different sites. Triparanol, for example, inhibits ∆ 24 -reductase an enzyme near the end of the biosynthesis pathway. Inhibition of this enzyme allows accumulation of desmosterol with induction of myotonia, a serious side effect.…”