摘要
采用7-氨基头孢霉烷酸(7-ACA)和AE-活性酯(MEAM)为原料合成3-乙酰氧基甲基-7-[2-(2-氨基-4-噻唑基)-2-甲氧亚胺基]-乙酰胺基-3-头孢-4-羧酸(头孢噻肟酸),并对副产物2-硫醇基苯并噻唑的回收工艺条件进行了探索研究,得到了一条清洁生产工艺.研究结果表明,合成头孢噻肟酸的较佳条件为:n(7-ACA)∶n(MEAM)=1∶1.1,二氯甲烷为溶剂、N,N-二甲基乙酰胺(DMAC)为催化剂和三乙胺(TEA)为促进剂,反应时间5 h,温度40℃,头孢噻肟酸收率85.9%,HPLC质量分数99.2%;副产物2-硫醇基苯并噻唑回收条件为:浸取温度70℃,浸取时间20 min,pH值3.0,精制溶剂为水和丙酮,回收率75.1%,HPLC质量分数98.8%,丙酮采用常压回收.头孢噻肟酸和2-硫醇基苯并噻唑产品结构经1H-NMR和FT-IR表征确认.
3-[ ( aeetyloxy ) methyl ]- 7- [ [ ( 2-amino-4-thiazoly ) ( methoxyimino ) acethyl ] amino ]-8- oxo-5-thia-l-azabicyclo[ 4,2,0 ] oct-2-ene-2-carboxylic acid (Cefotaxime) was synthesized from 7-amino-cephalosporanic acid (7-ACA) and 2 ( 2 aminothiazole-4-base)-( S)-2-methoxy imine ethylacyl sulfur generation benzothiazole (MEAM) and the conditions of recycling by-product 2(dH)-benzothiazolethione were also explored. A clean production technics was obtained. The optimal conditions for the synthesis of cefotaxime were obtained as following: n (7-ACA) : n(MEAM)= 1 : 1. 1, dichloromethane as solvent, N, N-dimethylacetamide (DMAC)as the catalyst, triethylamine as accelerant, reaction time 5 h and temperature 40 ℃. The yield of 7-AMCA was 85. 9% based on 7-ACA and the purity of HPLC was 99. 2%. The better conditions of recovering by-product 2(3H)-benzothiazolethione were found to be: leaching temperature 70℃, leaching time 20 rain, the pH of solution 3.0, acetone and water as refining solvent. The recovery yield of 2(3H)-benzothiazolethione was 75.1% and its HPLC purity was 98.8%. The structures of products were identified with ^1 H-NMR and FT-IR spectra.
出处
《浙江工业大学学报》
CAS
北大核心
2010年第1期7-10,共4页
Journal of Zhejiang University of Technology
基金
浙江省教育厅科研基金资助项目(20060798)