Research Of Industrial Preparation For Synthesizing Lumefantrine And Intermediate Based On Rough Fluorene

This paper mainly analyzed the content of fluorene by gas chromatography,by looking up literature and documents,analyzing the purification of fluorene and differ-ent synethsis of lumefantrine in previous process,pointing out their advantages and disadvantages and finally explored the synthesis process of lumefantrine which is sui-table for industrial production after rough fluorene being refined.There are some resp-ects of the main research contents:(1)The purification of industrial fluorene:compared the effect of different solvent on the purification of fluorene,discussed the recrystallization conditions of different solv-ents, analysed the yield and purity of fluorene and finally determined the best solvent.(2)Research of synthesis process for lumefantrine:compared the effect of different re-action temperature,reaction time,reaction raw material ratio,catalysts on synthesis of lumefantrine,and finally determined the best industrialized synthesis roues of lumefa-ntrine.(3)The purification of crude products lumefantrine:compared the effect of different s-olvent on the yield and purity of lumefantrine,and finally determined the best solvent.(4)The structure characterization and properties testing of each material:by testing the melting point,purity,nuclear magnetism to represent each material.The results of the study show that:(1) With the isopropyl alcohol as solvent and the crystallizing temperature was25-30℃,the effect on purification of fluorene is best.(2) The best synthetic route of lumefantrine was:with fluorene as the starting materi-al2,7-dichlorofluorene(intermediate Ⅰ)can be synthesized by the reaction of chlorin-ation between fluorene and chlorine with chloroform and glacial acetic acid as solve-nt;and then2-bromo-1-(2,7-dichloro-9H-fluoren-4-yl)ethanone (intermediate Ⅱ)can be synthesized by friedel-crafts reaction between2,7-dichlorofluorene and bromoace-tyl bromide with dichloromethane as solvent;(intermediateⅢ)2,7-dichlorofluor-en-4-oxirane can be synthesized by reduction reactions between sidium borohydride and intermediate Ⅱ with methanol as solvent;(intermediateⅣ)2-dibutyla-mino-1-(2,7-dic-hloro-9H-fluoren-4-yl)ethanol can be synthesized by the reaction between intermedia- te III and N-dibutylamine with N,N-dimethyl formamide as lacquer solvent,the target product(V):lumefantrine can be synthesized by the reflux reaction for about6hours between intermediateIV and4-chlorobenzaldehyde with methanol as solvent.(3)With the acetone as solvent,adding a little lacquer solvent and the crystallizing te-mperature was controlled in-5-0℃,the effect on purification of lumefantrine is best.This paper has the following innovation points:(1)In the process of refining of fluorene,the solvent will remove the impurities of fluorene which are bad for synthetizing lumefantrine,reaching the raw material requi-rements of fluorene by one time refining,greatly reducing the cost of industry.(2)Using the mixed solvent, not only chloridization can control the content of the chl-orine and trichlorine,but also improve the output.(3)In the process of refining of lumefantrine,with a unique refining process,which can enhance the purity up to99%,featured with simple and safe operation,possible for so-lvent recovery and reuse,low comprehensive cost.