Studies On Synthesis Of NXL-104 And The Mono Bromination Of Aniline Derivatives

The whole thesis is divided into two parts, including the synthesis of a novel ?-lactamase inhibitor avibactam(NXL-104) and mono bromination of aniline and its benzene derivatives.Part one is the synthesis studies of the novel ?- lactamase inhibitor avibactam. First, a review of the role?the type and the synthetic route of ?- lactamase inhibitors is given, and then we designed a improved synthetic route of avibactam, after the analysis of the synthetic routes at home and abroad. With L- pyroglutamic acid as a starting material, through protection, nucleophilic substitution to open ring, to oxime, cyclization, hydrogenation, sulfonated to form salt, a total of twelve-step reaction eventually synthesized NXL-104. The synthetic route improved the yield of the key reactions and the purification processes of several steps' reaction product were simplified. Compared with the methods reported in the literature the synthetic route has the advantage of high yield and easy to achieve amplification.Part two is focused on the mono bromination of aniline and its benzene derivatives. Direct bromination of aniline and its benzene derivatives has been achieved by the reaction with molecular bromine under low temperature, using propionic acid?methyl tert-butyl ether and triethylamine as buffer solvent. The monobromo compounds were obtained in good yield. Structure of the products was characterized by ~1H NMR. Compared with reported methods,this method suppressed side reactions,and one-half of the bromine atoms were recycled, avoiding the waste of bromine atoms and the harm to the environment. It's a simple, efficient, environmentally safe, and economical method for the mono bromination of anilines without metal catalysts, which makes it easy to realize large-scale production.