Preparation Of1,2,4-oxadiazoline Deirvatives, And Synthesis And Application Of Guanidine-Thiourea Bifunctional Organocatalysts

As a compound with excellent biochemical properties,1,2,4–oxadiazole has gottenmore and more attention in recent decades and can be applied in many areas, such asVirus resistance, cancer resistance, ionic liquids, oxidation resistance, growthregulation of plant and so on. Among them, drug synthesis is particularly significant.Nowadays the primary method to synthesize this kind of compounds includingoxidation of lead tetra acetate, electrochemical technique, application of acid chloride,1,3-dipolar cycloaddition and some other methods. Atom economy1,3-dipolarcycloaddition to synthetize1,2,4-oxadiazole derivatives was adopted in my paper.In the second chapter mentioned below, we screened the reaction conditionscomprising reaction substrates, reaction solvents, reaction temperature, reaction time,the dosage and sort of catalyst (Additive) etc. Finally we ascertained a conditionwhich could successfully avoid the use of metal complexes, triethylamine etc. thatallowing imide and chlorinated oxime as substrate, dichloromethane as solvent andstirring at room temperature for8hours without addition of any additives. Then weconducted a series of substrate and obtained a yield of up to53%.In the third chapter mentioned below, we have designed and synthesized a series ofguanidine-thiourea chiral bifunctional catalysts to catalyze1,3-dipolar cycloadditionreaction and get1,2,4-oxadiazole with single configuration in order to make1,2,4-oxadiazole derivatives a more important role in the synthesis of pharmaceuticals.Till now we have synthesized six kind of guanidine-thiourea bifunctional catalysts,and several other types of chiral catalyst successfully.In the fourth chapter mentioned below, we investigated all the catalysts referred in the previous chapter as well as several other catalysts to catalyze1,3-dipolarcycloaddition reaction, although the reaction conditions were optimized, there was nosatisfying results in chiral catalysis, what we obtained was an ee value which wasonly12.42. Then the bifunctional catalyst was applied to several other types ofreactions, but there was still no satisfactory result. For that reason we will try to find abetter catalyst for the synthesis of chiral2,4-oxadiazole, and will continue to try toapply bifunctional catalysts in more other types of reactions.