Design,synthesis And Antibacterial Activity Of Novel Pyrrole Alcohol, Pyrrole [2,3-d]pyridazine Compounds

Based on the P keto acid ester as initial raw materials, nine pyrrole esters compounds were synthesized firstly and then were oxidized to nine pyrrole aldehydes by ammonium cerium nitrate. Then the nine pyrrole aldehydes as the intermediates were divided into two synthetic routes. The first route is the eight pyrrole aldehydes were reduced by sodium borohydride to obtain eight pyrrole alcohols. The second route is the pyrrole aldehydes react with hydrazine hydrate to generate six pyrrole [2,3-d]pyridazine compounds. Among them the seventeen compounds are new compounds which are reported for the first time.The reaction process was monitored by thin layer chromatography (TLC). The structure of the compounds was identified and characterized through m.p., IR and 1H-NMR. Finally,preliminary antibacterial test of the six pyrrole[2,3-d]pyridazine compounds was conducted.The main contents as follow:1. Through consulting a large amount of relevant literature, the author described an overview of pyrrole derivatives and pyridazine derivatives, and put forward the research topic of this thesis.2. Using ultrasonic synthesis, nine pyrrole ester compounds were generated by knorr synthesis method in the solvent of HAc. Compounds through the structure characterization,were confirmed as the target products.synthesis contained two steps reaction, nitration was conducted in the low temperature, and cyclization reaction was generated controlled by ultrasonic synthesis(40 KHz, 500W, 65? ,0.5h), the method has the advantage of efficient,quick, safe and high yield.3. Nine pyrrole aldehyde compounds were generated, by using ammonium cerous nitrate as oxidant, in the solvent of THF-HAc-H2O. Compounds through the structure characterization, were confirmed as the target products.The ice water bath conditions combining greenhouse conditions were used in reaction. And the solvent system was optimized-the volume ratio of 4:4:4 for THF:HAC:H2O. Reaction yield and security were both improved.4. Eight pyrrole aldehydes were reduced by sodium borohydride as reducing agent to obtain eight pyrrole alcohols. Compounds through the structure characterization, were confirmed as the target products. This article used 1.2 eq. sodium borohydride, rapid and efficient synthesize of pyrrole in ethanol alcohol.5. Using ultrasonic synthesis, the pyrrole aldehydes reacted with hydrazine hydrate to generate six pyrrole[2,3-d]pyridazine compounds. Compounds through the structure characterization, were confirmed as the target products. Under ultrasonic irradiation (40 kHz, 200W) at 70? for about 0.5h, until the reaction is accomplished.The method has the advantage of efficient, quick and high yield .6. The author conducted bacteriostatic experiment for the six pyrrole[2,3-d]pyridazine compounds, using six strains including:staphylococcus aureus, pseudomonas aeruginosa,bacillus subtilis, soluble vibrio, escherichia coli and yeast.Results showed that the 6 pyrrole[2,3-d]pyridazine compounds had no antimicrobial activity for the selected strains.