Synthesis Of 2,3,4,5-tetrasubstituted Morpholine Derivatives Based On Aziridines

The aziridines are important intermediates and usually employed as useful building blocks for constructing versatile five-membered heterocyclic compounds, but the synthesis of polysubstituted morpholine derivatives based on non-activated aziridines are rarely reported. In this thesis, the synthesis of the aziridines and regioselectivity in the ring opening of non-activated aziridines were simply summarized in recent years, as well as the synthesis and application in medicament synthesis fields of the morpholine derivatives were also reviewed. The major works were as following:(1) ?-bromination reaction conditions were explored, and the optimal reaction conditions were got: molecular bromine as bromide reagent, methylene chloride as solvent, the yield is between 88% to 96%.(2) Referring to Gabriel-Cromwell reaction, 26 different 2-acylaziridine were prepared. The yield is between 85-95%. The influence of the electronic effect and steric-hindrance of the substituent on the N atoms on the aziridines synthesis were explored.(3) 16 various 2-aziridinemethanols were synthesized, and the yield is between 85%-92%. The stereochemical structure with threo configuration was determined by NOESY spectrum. It has high diastereoselectivity, dr>25:1.(4) Aza-Payne Rearrangement would happen if N atom contained the strong electron-withdrawing groups when the 2-aziridinemethanol carried on allylation reaction. Then the epoxy ethane derivatives were got.(5) 18 stable morpholine derivatives by the iodocyclisation reaction, hydrolysis reaction and elimination reaction were synthesized, and the influence of steric-hindrance of the substituent on the iodocyclisation reaction was explored. The stereochemical structure was determined by NOESY and HSQC spectrum, dr>25:1.