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

1,2,4-Oxadiazoles derivatives, belonging to five-member heterocyclic compoun- ds, often act as the effective active groups in design of new drugs and agricultural chemicals. They have many kinds of biological activity, such as antibacterial, antihypertensive, insecticidal and herbicidal et. al.The derivatives of strobilurin are extensively applied in the agricultural chemicals, they may be used to prevent and control the powdery mildew, rust disease, the net spot sickness, the frost mildew, the rice blast and so on. The derivatives of piperazine and benzopyran have extensive applications in drug synthesis, because they have multi- biological activities, such as antianaphylaxis, sterilization, anticancer, the anti hypertension and so on. In this thesis, according to principles of hybridization and bioisosteric replacement,three categories total amount of fifteen novel compounds are designed and synthesized, which contain the 1,2,4-oxadiazoles strobilurin derivatives, 1,2,4-oxadiazoles piperazine derivatives, as well as 1,2,4-oxadiazoles benzopyran derivatives.(Un)substituted benzamidoximes(5a~5f) were obtained by (un)substituted benzonitriles(6a~6f) reacting with hydroxylamine hydrochloride. Then the compound (5a~5f) reacted with chloroacetyl chloride to give 5-chloromethyl-3-[(un)substituted phenyl]-1,2,4-oxadiazoles(4a~4f). Methyl {2-[(3-(un)substituted phenyl-1,2,4-oxadia- zol-5-yl)methoxy]phenyl}acetate(7a~7f) were obtained by methyl (2-hydroxyphenyl) acetate reacting with the 4a~4f.The 7a~7f reacting with N,N-dimethylformamide 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~1e).2,6-Dimethylaniline reacted with chloroacetyl chloride to product the 2-chloro- N-(2,6-dimethylphenyl)acetamide. The latter reacted with piperazine to give 4-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine, which reacted with 4a~4f to obtain compound 1-[(2,6-dimethylphenyl)aminocarbonylmethyl]-4-{[3-( (un)subst-...