Asymmetric Synthesis Of ¦Á-amino Phosphoric Acid Diethyl

It is obtained that the ratio of R / S configuration ofα-aminoethylphosphite with the peak area of 31P NMR integral.α-aminoethylphosphite configuration subjects to certain catalysts (for example: boron trifluoride diethyl ether and aluminum chloride) in large.Under these of other catalysts is smaller (such as: Tie chloride, the Tie chloride, zinc chloride, and so on). The result is mainly R configuration. This is because the boron trifluoride diethyl ether and aluminum chloride can make a "complex role," with the benzene ring in imine. This changes the conformation of the transition state.Ethyl phosphate attacks to the C = N bond from space in less resistance, this changes the direction of addition. S configuration is the main product.With the increase of catalyst, it is upward trend of the stereoselectivity of addition reaction of ethyl phosphite to imine.Different solvents have greater impacts on the stereoselectivity of addition reaction.This is because some solvents can enhance complexation between benzene ring and the catalyst. The ratio of S configuration increases. In addition, some solvents make the complex role weakening, not to change the direction addition, R configuration is still main.We study the electronic effect of the substitute in Benzene ring on the impact of three-dimensional selectivity.And choose Cl and CH3O as replacement of imine to compare H substituted of imine.Found that the impact of the benzene ring substituted is very small to three-dimensional selectivity.This is mainly because the aromatic and C = N double bond in the same plane,substitute little impacts on△△G≠in the transition state.Inspected the temperature on the impact of stereoselective of the Addition. At low temperature, the reaction controled by the dynamic. Ethyl phosphite attacks from the small space resistance in the direction, R configuration is the main product.At high temperature, the reaction controled by the thermodynamic.Ethyl phosphite still attacks resistance from the high space resistance in the direction.S configuration is main.With the increase of temperature , the ratio of S configuration of the product is gradually increasing.The second part of the work: We mainly synthesize the intermediates of fentanyl compound.According to literature,we synthesize N,N-di-(β-methyl propionate) benzylamine,1-Benzyl-4-piperidone,4-(Phenylamino)-1-(phenylmethyl)-4-piperidinecarbonitrile,4-(Phenyl-amino)-1-(phenylmethyl)-4-piperidinecarboxamide.Improving test conditions of the intermediates.Shortening the test time,increasing work efficiency and increasing the yield. For example,we prepared crude products of N,N-di-(β-methyl propionate) benzylamine for the next step, yield up to 79%,avoiding it lost during vacuum distillation.