Research And Application Of New Methods Of Phosphoramide Synthesis

Among the organophosphorus compounds,phosphoramide is a kind of valuable multifunctional molecule,which is widely used in biomedicine,agriculture,industry and organic catalysis.At present,the known methods for synthesizing phosphoramides are generally divided into five categories according to the different substrates used: 1)Synthesizing phosphoramides with phosphorous halides as substrates;2)Synthesizing phosphoramides with phosphoric acid compounds as substrates;3)Synthesizing phosphoramides with phosphorous hydrogen compounds as substrates;4)Synthesizing phosphoramides with azides as substrates;5)Other methods.However,the known methods for synthesizing phosphoramids either need to use phosphorus halogen or phosphorus hydrogen compounds that are very sensitive to air and water,or need to be carried out smoothly under conditions such as high temperature,strong alkali or metal catalysis.There are many side effects and the application scope of substrate is limited.Therefore,the development of a mild,green,economic and efficient method for the synthesis of phosphoramide compounds has very important theoretical and application value.This thesis consists of the two parts as below:First,synthesis of N-acyl phosphoramides by a novel Staudinger reaction.This method takes acyl diphenyl(or alkyl)phosphorus and azide compounds as substrates without any additives and catalysts,takes nitrogen as the only by-product,and obtains a series of new acyl phosphorous amides containing various amino acids,natural products and chiral binaphthyl skeleton through the cutting of C-P bond,and a series of new organic phosphorus compounds are further obtained through derivative reactions such as oxidation,reduction and substitution.The obtained chiral acyl phosphoramides can be used as new chiral ligands to catalyze the asymmetric Knoevenagel reaction between 2-methylphenylacetaldehyde and diisopropyl malonate.In addition,the reaction can also be used as a new synthetic route of valsartan(antihypertensive drug)intermediate.Second,under the action of alkali,a series of new N-acyl phosphoramides containing various amino acids,natural products and drug molecular skeleton were synthesized by three-component "one pot" method with carboxylic acid,trivalent phosphorus chloride and azide compounds as substrates,so as to realize the simple synthesis of oxa,aza and thiacyclophosphamides,some known drug molecules and bioactive compounds were synthesized.The correlation between the two parts is that the N-acyl phosphorous amide products obtained in the previous reaction can be oxidized to obtain the N-acyl phosphoramide products of the next reaction.The main purpose of this study is green,mild reaction and high atomic economy.It provides innovative theoretical and applied research value for the synthesis of N-acyl phosphoramides and N-acyl phosphoramides,provides a new method for the synthesis of phosphorus containing drug molecules or intermediates,and provides a new idea for the modification of amino acids,natural products and drug molecules.