Green N-Formylation And N-Methylation Of Amines

Green chemistry is a requirement of social development and the chemical industry.The N-formylation and N-methylation of amines are widely used in the synthesis of many important chemicals,biological intermediates and drugs.Traditional N-formylation and N-methylation of amines require the use of carbon monoxide,diazomethane,methyl iodide and other highly toxic and environmental unfriendly formylation or methylation reagents.The development of environmental friendly green formylation and methylation reaction systems have become a hot spot of current research.In this article,carbon dioxide and methanol are used to replace the traditional formylation and methylation reagents,respectively,and the green N-formylation and N-methylation reaction systems of amine compounds are developed respectively.In line with the concept of green chemistry,we can obtain corresponding products with high selectivity,and have important academic value and practical application potential.For the study of the green N-formylation of amines,the greenhouse gas carbon dioxide was used as the formylation reagent,inexpensive sodium borohydride and ammonium sulfate were used as the hydrogen source,and triethylamine as the added base to achieve N-formylation of amines under mild conditions.The optimized reaction system had good substrate applicability,and a highly efficient N-formylation reaction of 14 amine substrates was achieved with a maximum separation yield of 86%.In addition,the reaction mechanism was explored through NMR,and it was observed that the generation of NH₃BH₃ and the H₃-_mB?OCOH?_m intermediate formed by the insertion of carbon dioxide between B-H.According to the experimental results and previous studies,the possible reaction path of N-formylation reaction of amines in this system was proposed.During the catalytic reaction,the boron reagent acted as a Lewis acid to activate carbon dioxide,which played a vital role in the conversion of formylation.For the study of the green N-methylation of amines,a series of iridium complexes containing amide ligands were synthesized,using inexpensive and easily available methanol as the methylation reagent and cesium carbonate as the added base,and successfully achieved the N-methylation of amine compounds.Using this method,some N-methylated products can be synthesized with high selectivity.The catalytic system had high atom economy,and the only by-product was water,which was a green and economic N-methylation method.At the same time,the catalytic system had good substrate applicability,and achieved efficient conversion of15 amine substrates under optimal conditions,with a maximum separation yield of 99%.In addition,the mechanism was explored by NMR and control experiments.The important reaction intermediates such as imine and formaldehyde were detected,and it was confirmed that the formaldehyde content in the catalytic system had an important effect on the selectivity of catalytic reactions,and the reaction followed the hydrogen reaction mechanism.On this basis,the catalytic reaction mechanism of N-methylation of amines was proposed.Metals and ligands cooperated to achieve the N-methylation reaction of amine substrates.