Study On Syntheses Of O-Hydroxylphenyl-aryl Bridge Compounds And The Test For Their Biological Activities

In recent years, various infectious diseases caused by germina broke frequently due to lack of safe and effective microbicides. Therefore, to research new efficient antibacterial agents has become an urgent international issue.In this paper, triclosan with specific sterilization as template molecule, a series of o-hydroxylphenyl-aryl bridge compounds were designed and synthesized based on bioinformatics and bactericidal mechanism. Furthermore, the characterization and antibacterial activities of the compounds were studied.Firstly, three compounds of chloro-o-hydroxyl-diphenyl-ether and their intermediates were synthesized. The characterization was confirmed by IR, 1HNMR and element analysis. The reaction kinetics of chloro-phenol with 2,5-dichloro-nitrobenzene, the relation between the structure of chloro-phenol and reaction activity, the rules of phase transfer catalyst effection were obtained. The conversion effection of the substituted groups, metal cations on o-amino-diphenyl ether diazonium salt were studied. The intramolecular cyclization mechanism of this kind diazonium salt under metal cation as catalyst were proposed firstly.Secondly, the process of preparing chloro-o-hydroxyl-dipheyl ether was designed in this paper. Combination purification technology include excimer rectify, complex extraction, removal of metal cation, muti-step extraction was proposed firstly. As a result, the first technology for preparing o-hydroxyl-dipheyl ether was built in domestic.Thirdly, the four compounds of o-hydroxylphenyl-benzyl-amine and their intermediates were synthesized, and their character was determined by IR, 1HNMR. The reaction of benzyl halide with o-amino-phenyl-methyl ether to produce N-benzyl compounds, and demethylation of o-benzyl-amino-phenyl-methyl ether were studied. The rules of the effection of nucleophile of substituted groups, the reaction media, conditions on the yields of products were studied also.Finally, the tests of antibacterial showed that colibacillus, staphylococcus aureus, candida albicans, pseudomonas aeruginosa were restrained by triclosan; candida albicans, colibacillus, staphylococcus aureus were restrained by 2-amino-benzyl- -phenol, 2-(4-chlorobenzylamino)-phenol; colibacillus, staphylococcus aureus were restrained by 2-(4-hydroxyl)benzylamino-phenol also. The oral test of mice and rats, bone marrow in red cell nuclear test of mice, skin irritation test, etc. showed that triclosan is of low poison and no irritation.