Study On The Synthesis Of 1,2,4-Oxadiazole Derivatives

In the research and development of drugs and agricultural chemicals, whatever synthesized heterocycle compounds or heterocyclic natural products play a very important role. In all of heterocycle compounds, 1,2,4-Oxadiazoles containing nitrogen and oxygen have much more importance. 1,2,4-Oxadiazoles have extensive bioactivity, such as antibacterial, herbicidal, insecticidal, miticidal et al. in the agricultural chemicals and antiinflammatory, hypolipidemic, anticancer, antihyperten-sion, antianaphylaxis et al. in drugs.In the design of drugs and agricultural chemicals, bioisosterism is one of very important methods modifying and optimizing leading compounds. Modified and optimized products have much more selectivity, higher bioactivity, lower side effects. Hybridization is a method of combining two or more active structure units by chemical bond into one molecule, and then the resulting molecule entity has more strong efficacy and lower side effects. In this thesis, according to principles of hybridization and bioisosteric replacement, three categories, total amount of twenty nine novel compounds are designed and synthesized, which contain the 1,2,4-oxadiazole strobilurin derivatives, 1,2,4-oxadiazole piperazine derivatives, as well as 1,2,4-oxadiazole benzopyran derivatives.(Un)substituted benzamidoximes(5a～5k) were obtained by (un)substituted benzonitriles(6a～6k) reacting with hydroxylamine hydrochloride, Then compounds (5a～5k) reacted with chloroacetyl chloride to give 5-chloromethyl-3-[(un)substituted phenyl]-1,2,4-oxadiazoles(4a～4k), Methyl {2-[(3-(un)substituted phenyl-1,2,4-oxadi-azol-5-yl)methoxy]phenyl}acetate(7a～7k) were obtained by methyl (2-hydroxyphen-yl) acetate reacting with the 4a～4k.The intermediate(7a～7k) reacting with N,N-dirnethylformamide dimethyl acetal (DMFA) gave methyl 3-dimethylamino-2-{2-[2-(dimethylamino)-1-(3-(un)substituted phenyl-1,2,4-oxadiazol-5-yl)vinyloxy]phenyl}acrylate(1a～1k).2,6-Dimethylaniline reacted with chloroacetyl chloride to produce the 2-chloro-...