Construction Of Fluorinated Alkyl Nitrogen Heterocyclic Compounds Using Fluoroalkyl Imine Derivatives As Building Block

Nitrogen heterocyclic compounds are widely used in medicine,agricultural chemical,materials and other fields due to their particular biological activities.The introduction of fluoroalkyl groups into drugs candidate can often change their lipid solubility,acid-base properties,and chemical stability as well as increase their molecular bioavailability.Therefore,the introduction of fluorine-containing groups into drugs has become a routine and effective means in the process of drug development and agrochemicals discovery.Compared with the synthesis of conventional nitrogen heterocycles,there are relatively few studies on the synthesis of nitrogen heterocycles containing fluoroalkyl groups.Fluoroalkyl imine derivatives are an important class of synthons with the characteristics of simple preparation,stable structure,wide range of substrates,and high reactivity.Therefore,it is of great significance to design and synthesize new fluoroalkyl ammonia derivatives and use them as starting materials to construct fluoroalkyl nitrogen heterocyclic compounds.The paper mainly introduces the following works:(1)The application background of haloalkyl nitrogen heterocyclic compounds in the treatment of cancer,tumor,diabetes,AIDS and other diseases,as well as in the weeding,sterilization,insecticidal and other aspects was reviewed.In addition,the synthesis of fluoroalkyl substituted nitrogen heterocycles and the synthesis of fluoroalkyl acetylimide derivatives were also introduced.(2)Have developed a mild,efficient and metal-free method for the synthesis of 2-perfluoroalkyl quinozalines,through a visible-light-mediated radical cascade arylation/cyclization reation of fluorinated imidoyl isothiocyanates and aryl diazonium salts.The mechanism experiments have verified that the reaction undergoes a free radical chain reaction initiated by Eosin B.The reaction is easy to operate and has high functional group tolerance,providing a rapid and direct method for the synthesis of 2-trifluoromethylquinazoline compounds.(3)Faclitated by light and alkali,have attempted to construct 2- difluoroalkylbenzimidazoles using a simple and readily available 2-bromo-2,2-difluoro-N-methyl-N’-(p-tolyl)-N-tolylsulfonamide by Smiles rearrangement and intramolecular free radical cyclization reactions.The reaction conditions have been initially explored,and further experimental investigations are still ongoing.