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

1,2,4-Oxadiazoles belong to five-membered heterocycle compounds. Because of the existence of oxygen and nitrogen in the structure, the 1,2,4-oxadiazoles have high affinity and selectivity to the ligands. Therefore, the derivatives of 1,2,4-oxadiazoles are widely used in medicine and pesticide.The derivatives of strobilurin have showed better effects on curing powder mildew, rust disease and rice blast. Hence the strobilurin has been an active group in the pesticides. The derivatives of piperazine and benzopyran play essential roles in new drugs development, such as antianaphylaxis, sterilization, anticancer and antihypertension. In this thesis, fourteen novel compounds which contain 1,2,4-oxadiazoles are designed and synthesized on the base of hybridization principle and bioisosterism.(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 intermediate(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(la~le).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 l-[(2,6-dimethylphenyl)aminocarbonylmethyl]-4-{[3-( (un)subst-ituted phenyl)-1,2,4-oxadiazol-5-yl]methyl}piperazine(2a~2f).The 7a. 7c and 7e were intramolecularly condensed in the existence of sodium methoxide, which produced 2-(3-(un)substituted phenyl-l,2,4-oxadiazol-5-yl)-4H-1-benzopyran-3-ol(3a,3c and 3e).The structures of three series of 1,2,4-oxadiazole derivatives have been confirmed by elemental analyst, IR, and !H-NMR.The microstructure and interaction of the molecules for the chemical substances can be investigated at atomic level by single crystal analysis, which is one of important technological tools in the research of modern chemistry. In this thesis, we obtained the crystal often compounds and the crystal structures were characterized by XDR. From the X-ray analysis, we know that the single crystal is in monoclinic space group P2]/c for 4f, 7b, Id and 2b, triclinic space group P-l for 7a, 7e, la and lc, monoclinic space group P2i/n for le and 3a.