In Situ Synthesis Of ?-amino Ketone By Continuous Heyns Rearrangement From ?-hydroxy Ketone

Nowadays,organic chemistry has provided many synthetic methods for natural products and complex compounds.With the deepening of research,how to synthesize complex compounds efficiently and economically has attracted more and more attention.Meanwhile,green chemistry has become an important direction of organic chemistry research.Amino ketones are a kind of natural products and widely existing in drug skeletons.Among them,?-amino ketones are an important kind of amino ketone compounds.Due to the special?position amino substituent,?-amino ketones have a lot of special properties.Heyns rearrangement was first found in the synthesis of ketose.It has the advantages of green economy and fewer by-products.Recent studies have shown that Heyns rearrangement is not only suitable for ketose,but also for the synthesis of?-amino ketone.Traditional?-amino ketones are usually synthesized by metal catalysts or halogenated reagents.In production,sewage containing metal ions or halogen ions are inevitably produced.Sometimes complex metal ligand catalysts are used,the cost is too high to be extensively applied.With the development of the chemistry,the synthesis of organic compounds has new requirements.Green sustainable development and atomic economic reaction are paid attention to.Therefore,an economical and green method for the synthesis of?-amino ketone is urgently needed.We have developed a new one-step green synthesis method of?-amino ketone.Using?-hydroxyl ketone and various secondary amines as raw materials and p-toluene sulfonic acid as catalyst,the corresponding?-amino ketone was obtained by heating for 16 hours at 50~oC.Moreover,the reaction does not require solvents,and the only by-product is water.All the reaction products were confirmed by strictly characterization.Heyns rearrangement product was first obtained,and continues reacted with amine to form diamino substituted intermediates.Secondly,the intermediate is hydrolyzed and a part amine is removed to obtain a substituted product at the?-position by amine.Finally,the reaction result seems that the hydroxyl groups on the substrates were replaced by amino group directly.This synthetic method further extends traditional Heyns rearrangement,and enriches the content of traditional Heyns rearrangement.