RESUMO
A metal-free one-pot strategy has been developed for the first time to synthesize pharmaceutically important α-amino ketones from readily available benzylic secondary alcohols and amines using N-bromosuccinimide. This new reaction proceeds via three consecutive steps involving oxidation of alcohols, α-bromination of ketones, and nucleophilic substitution of α-bromo ketones to give α-amino ketones. Importantly, this novel one-pot greener reaction avoids direct usage of toxic and corrosive bromine. This methodology has been employed efficiently to synthesize pharmaceutically important amfepramone and pyrovalerone in a single step.
Assuntos
Álcoois/química , Bromosuccinimida/química , Cetonas/síntese química , Aminas/química , Catálise , Dietilpropiona/síntese química , Dietilpropiona/química , Halogenação , Cetonas/química , Estrutura Molecular , Oxirredução , Pirrolidinas/síntese química , Pirrolidinas/química , EstereoisomerismoRESUMO
The direct α-amination of ketones, esters, and aldehydes has been accomplished via copper catalysis. In the presence of catalytic copper(II) bromide, a diverse range of carbonyl and amine substrates undergo fragment coupling to produce synthetically useful α-amino-substituted motifs. The transformation is proposed to proceed via a catalytically generated α-bromo carbonyl species; nucleophilic displacement of the bromide by the amine then delivers the α-amino carbonyl adduct while the catalyst is reconstituted. The practical value of this transformation is highlighted through one-step syntheses of two high-profile pharmaceutical agents, Plavix and amfepramone.
Assuntos
Aminas/química , Ticlopidina/análogos & derivados , Aldeídos/química , Brometos/química , Catálise , Clopidogrel , Cobre/química , Dietilpropiona/síntese química , Ésteres/química , Ticlopidina/síntese químicaRESUMO
The Reference Standards for amfepramone, cathinone, N-ethylamphetamine, fenethylline, fenproporex and mefenorex were prepared. Their purities determined by HPLC were more than 99.5%. For the identification and determination of these six drugs, their analytical data were measured and discussed by TLC, UV, IR, HPLC, GC/MS and NMR.