The Synthesis And Antibacterial Activity Of Pyridine Compounds And Chlorothalonil Analogues

Pyridine compounds are a kind of natural nitrogen heterocyclic compounds that widely exist in the nature.Meanwhile,pyridine sketon widely exists in synthetic drugs and has important biological activities.Fluorine-containing compounds play an important role in the life that attribute to metabolic stability and binding affinity of fluorine atom.Based on the pharmacological activity of the pyridin-2-ones?pyrimidin-4-ones?and fluorine-containing pyridines,this paper develops one-pot method synthesis of two kinds of pyridine compounds,then the biological activity of the pyridines was studied.Drug susceptibility testing is designed to know the sensitivity of pathogenic microorganism to drug and that can rational guide to use antibacterial agents in agricultural clinical microbiology tests.Based on chlorothalonil's anti-bacterial activity,a kind of chlorothalonil analogues was designed and synthesized,and their antibacterial activity was comprehensively tested.The first chapter,a mini review was discussed that about the application of the pyridin-2-ones,pyrimidin-4-ones,fluoride pyridine compound,chlorothalonil analogues and test methods of antitumor and antibacterial activity of these compounds.The second chapter,an efficient and concise method to selective synthesize pyridin-2-ones and pyrimidin-4-ones by the reaction of 1,1-enamines 1?EDAMs?react with dimethyl sulfur aldehyde 2 under the conditions of CH₃CN as solvent,Cs₂CO₃ as alkali.The antitumor bioactivity screening shows that some compounds have potent antitumor activity.Especially,compound 3r,shows the most potent activity with IC₅₀values lower than 12.3?mol/L against four human tumor cell lines,making it more active than cisplatin?DDP?.In addition,an efficient,environment friendly and highly selective synthesis of protocol was constructed.This method is three-component one-pot reacton of N-mono-substituted 1,1-ene diamines?MEDAMs?1,benzaldehyde derivatives 2,active methylene dicarbonyl compounds 3.The third chapter,a concise method to synthesis of analogues of chlorothalonil was constructed that through the reaction of polyhalo isophthalonitrilesre with benzyl amines in 1,4-dioxane or CH₃CN promoted by K₂CO₃.The antibacterial activities were widely screened and found that some compounds have excellent antibacterial activities than that of marketable drug chlorothalonil.The structures of the target compounds were characterized by ¹H NMR,¹³C NMR,IR,HRMS and other spectroscopic methods.The single crystals of some of the compounds were determined by X-Ray single crystal diffraction.The structure of the compounds was confirmed.