【作者】 陈磊；

【导师】 高忠良；

【作者基本信息】 河北工业大学 ， 应用化学， 2006， 硕士

【摘要】 课题主要研究了吉米沙星的化学合成,吉米沙星是一种新氟喹诺酮类抗菌剂,其化学名为:7-(4-氨基甲基-3-甲氧亚氨基吡咯烷-1-基)-1-环丙基-6-氟-4-氧代-1,4-二氢[1,8]二氮杂萘-3-羧酸,是由母核和支链经取代反应连接而成的。 母核化学名为:7氯-1-环丙基-6-氟-4-氧代-1,4-二氢[1,8]二氮杂萘-3-羧酸。由于吉米沙星母核为萘啶结构,与以往沙星母核的喹啉和吡哌结构的区别在于1—位用N代替了C,所以课题结合反应机理对母核合成的实验条件和试剂进行了改进和优化。酰氯化反应优化工艺条件为:亚硫酰氯与氟氯烟酸的投料比为1.8:1,以二甲基甲酰胺为催化剂,甲苯作溶剂,加热回流6h,收率:88.7%;酯化反应优化工艺条件为:丙二酸二乙酯与2,6-二氯-5-氟-吡啶-3-酰氯的投料比为1.07:1,50℃搅拌2h。收率82.1%;脱羧反应优化工艺条件为:对甲苯磺酸为催化剂,水作溶剂,加热回流10h。收率57.1%;合环反应优化工艺条件为:控制PH值为9,以DMF作为溶剂,温控125℃加热1h。收率95.1%。 支链化学名为:4-氨基甲基-3-甲氧亚氨基吡咯烷二三氟乙酸盐。课题在前人的研究基础上对7位支链的合成中的环合反应进行了改进:金属钠为环合剂,戊醇为引发剂,温控40℃以下加热3h。收率71%。 应用螯合法将吉米沙星支链与母核接合,并对反应的溶剂和脱酸剂进行了重新选择,得到了良好的收率。优化的工艺条件为:反应时间为5h,反应的较佳温度为60℃,DMF为反应溶剂,碳酸钾为脱酸剂。收率47.3%。 实验中对各中间体进行了红外吸收光谱,核磁共振氢谱,质谱等的表征,结果表明各产品的化学结构与目标产物相符,证明实验路线合理可行。更多还原

【Abstract】 The work of tins research is devoted to the synthesis of gemifloxacin, chemical name: 7-（4-aminomethyl-3-methyloxyiminopynolidim-1-yl）-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid, it’s jointed by the naphthyridine nucler and the branched-chain.Naphthyridine nucler’s chemical name : 7-chlor-l-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid.Because of the difference between Gemifloxacin’s nucler and others before,using N instead of C in direction-1, this work improved the yield and purity of the product with reactive mechanism, The appropriate reaction conditions of chlorobenzene reaction : the proportion of socl₂ and 2,6-dichloro-5-fluoro-nicotine acid is 1.8:1.N N-dimethylformamide as catalyzer,toluene as solvent,reaction time: 6h,the yield achieved 88.7%, The appropriate reaction conditions of esterisy reaction: the proportion of Diethyl Malonate and 2,6-dichloro-5-fluoronicotinoyl chloride was 1.07:1. reaction time:2h,reaction temperature:50 ℃ . the yield achieved 82.1%, The appropriate reaction conditions of decarboxylation reaction: p-toluene sulfonylchloride as catalyzer,water as solvent, reaction time:10h, the yield achieved 57.1%, The appropriate reaction conditions of cyclization reaction:PH=9, DMF as solvent, reaction temperature:125℃. reaction time:lh .the yield achieved 95.1%.7-branched-chain’s chemical name : 4-amiriomethyl-3-methyloxyiminopynolidin ,we improve and imagine the 7-branched-chain on the base of other people.The appropriate reaction conditions of cyclization reaction:Na as cyclization reagent, Isopropyl alcohol as initiator, reaction temperature:40℃. reaction time:3h. the yield achieved 57.1%.Jointing the two parts by means of the borate chelate first time,and choosing another solvent,and got a better yield. The appropriate reaction conditions of gemifloxacin: reactiontemperature:60°C. reaction time:5h, DMF as solvent,K2CC>3 as acid removal agent, the yieldachieved 43.7%The intermedias were characterized by IR spectra, MS spectra ’H-NMR spectra, the elemental analysis, the results showed that the structures of products were the same to the target compounds. The result prove that the route of the reaction is sound with better reactcondition.更多还原