Dissertation > Industrial Technology > Chemical Industry > Pharmaceutical chemical industry > Antibiotics manufacture

The Process Improvement of Pipemidic Acid

Author CuiTao
Tutor HuangLongJiang
School Qingdao University of Science and Technology
Course Chemical processes
Keywords pipemidic acid quinolones antimicrobial agent synthetic improvem-ment
Type Master's thesis
Year 2013
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Pipemidic acid belongs to quinolones is a synthetic antibacterial agent.It has exhibi ted antibacterial activity mainly against gram negative bacteria such as pyocyanin, eschenchia coli,proteobactria and klebsiella pnenmoniae.lt is also effective on some gram positive bacteria.lt is more active than Nalidixic acid,Piromidic acid,Cephalexin and Ampicilin. In addition,pipemidic acid did not show toxicity and drug resistance compared with other antimicrobial drugs,this drug has been widely used in treatment of diseases both of the systemic and urinary tracts infections.Relating to the preparation of Pipemidic Acid, the national synthetic routes used4-chloro-pyrimidin-5-carboxylic acid ethyl ester as the raw material, In comparison, the route is more advanced level, but there are some disadvantages such as low yield, high cost, much three wastes. This thesis focuses on the lack of the route, We analyzed the key reaction steps(chloration reaction, Diekelmann cyclization reaction, piperazine’s condensation reaction) in the process route which affect the yield and produce large amounts of waste,and modified those steps, obtained a yield increased, cost reduction, waste reduction process route.In this thesis, the specific job done as follows:(1) chloration reaction:Compared to the original route, we used DMF as catalyst, Not only reduced amount of phosphorus oxychloride and triethylamine hydrochloride, shortened the reaction time but also improved the yield of the reaction, reduced the discharge of waste; The appropriate reaction conditions:Et3N.HCl was0.5mole aq.;POCl3was2.25mole aq.,DMF was0.1mole aq; refluxing time was7h,the yield achieved88.9%Compared to the original process yield increased by5.6%.(2) Diekelmann cyclization reaction:studied the effect of different bases on the cyclization yield, And eventually found using tert-butoxide in place of potassium isopropanol, t-butanol instead of isopropanol as solvent, the cyclization yield the highest yield, the yield achieved92.9%, Compared to the existing potassium isopropoxide cyclization reaction, the yield was improved by7.33%。(3) condensation reaction:piperazine was3.25mole aq., the yield achieved 81.2%.In addition, this thesis drawed and explored three synthesis routes for Pipemidic Acid’s framework according to the known synthestic methods of quinolone’ frameworks especially of gatifloxacin drugs, but were unable to obtain succes

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