Research On The Preparation Of New Fluorinating Reagent And Its Application To The Synthesis Of Fluoropyridazines

Because of high bioactivity property of fluoropyridazines,which have bactericidal,antiviral,insecticidal,weeding affection,research on their synthesis has attracted much attention from field of medicine and drug R&D. Exchange of halogen atom was one of important fluorination methods to synthesis fluoropyridazine derivatives.In this paper,two novel class of fluorinated reagents were designed and prepared.On this base,we carried out the fluorination reaction of halogenated pyridazinones,that provided a series of fluorinated pyridazine derivatives.This dissertation consists of two main parts:1.Synthesis of fluorinating agent(1) Synthesis of ethylhexamethylenetetramine fluoride:Firstly,ethylhexamethylenetetramine bromide was synthesized from bromoethane ethylhexamethylenetetramine.A two-step sequent ionexchange reaction took place after that.The amount of fluoride ion was analyzed by fluoride ion electrode,that date was close to the caculated one, it means that the structure was just what we expected.(2) Synthesis of fluorin-supporting resin:A new fluorination reagent was prepared by modify the structure of D301 resin.IR spectroscopy analysis and evaluation of the amount of fluoride ion were combined together to determine the structure of target products.2.Flurination of halopyridazinonesWe have developed a new and efficient green synthetic procedure for the synthesis of fluoropyridazines with fluorin-supporting resin and ethylhexamethylenetetrarnine fluoride as fluorination reagent.The best reaction conditions are summarized as follows:a.Temperature:100℃;time:10h;Solvent:DMSO;n(ethylhexame-thylenetetramine fluoride):n(pyridazines) = 3:1.b.Temperature:140℃;time:14h;Solvent:DMSO;n(fluorin-supporting resin):n(pyridazines) = 4:1.On this base,we have synthesized a series of fluoropyridazines.