N-H Insertion Reaction Of Glycine Ethyl Ester With Amine Compounds Catalyzed By Metalloporphyrins

C-N coupling studies are particularly important because C-N is widely found in pharmaceutical intermediates,natural products and polymer polymers.N-H insertion has become an important way to achieve C-N coupling.It was found that in the N-H insertion reaction system,carbene is generally derived from diazo compounds,but did not find the use of glycine ethyl ester as the source of carbene with aniline to carry out N-H insert reaction.Therefore,this paper explores the N-H insertion reaction of amine compounds with glycine ethyl ester as carbene source,and achieves C-N coupling of glycine ethyl ester with amine compounds.The main contents of the experiment are as follows:(1)The conditions of N-H insertion reaction of metalloporphyrin-catalyzed aniline were optimized with glycine ethyl ester and aniline as reaction materials.Through the systematic study on the catalyst,the kind of acid,the temperature,the solvent and the substrate equivalent,it was found that the optimum conditions were as follows:tetraphenyl iron porphyrin(2.5mg),dichloromethane:water ?1:1,Acetic acid(0.45 mmol),sodium nitrite(0.45 mmol),glycine ethyl ester(0.45 mmol),and aniline(0.3 mmol).When the substrate is a smaller primary amine 20? is the optimum reaction temperature for the reaction;when the substrate is secondary amine and steric larger primary amine,70 ? is the optimum reaction temperature for the reaction.(2)The amines scope has been studied under optimum condition.The results showed that the N-H insertion reaction catalysted by metal porphyrin has a wide range of applications.Both primary and secondary amines can undergo N-H insertion reactions with glycine ethyl esters.(3)Preliminary Study on the Mechanism of N-H Insertion of Ethyl Alcohol and Amine Compounds Catalyzed by Metalloporphyrins.The experimental phenomena in the optimization of the conditions and the GC-MS monitoring of the reaction showed that there was the presence of ethyl diazoacetate in the reaction.The reaction may be that the glycine ethyl ester is in situ to produce ethyl diazoacetate and then combined with the metal porphyrin to form the metal carbene,and finally the metal carbene is subjected to the N-H insertion reaction of the amine compound.