摘要
以 6 氨基青霉烷酸为原料 ,经多步化学反应合成了他唑巴坦并重点研究了其中的 1,3 偶极环加成反应。首先由 6 氨基青霉烷酸通过重氮化 -溴化、氧化、保护、还原去溴得到了青霉烷酸二苯甲酯亚砜 ,每步反应的收率都在 90 %以上 ,然后与 2 巯基苯并噻唑反应得双硫开环物 ,收率为 99% ,再分别与无水氯化铜、叠氮化钠、高锰酸钾反应得到 2 β 叠氮甲基青霉烷酸二苯甲酯二氧化物 ,三步总收率为 30 % ,接着以醋酸乙烯作为环合试剂进行 1,3 偶极环加成反应制得 2 β 三唑甲基青霉烷酸二苯甲酯二氧化物 ,收率为 70 % ,最后经间甲酚脱保护得到了他唑巴坦 ,收率为 6 3%。整个反应经中试放大 ,总收率达 8.0
Tazobactam was obtained from 6-aminopenicillanic acid through multistep reactions. The 1,3-dipolar cycloaddition was studied emphatically. Firstly, 6-aminopenicillanic acid was converted to benzhydryl penicillanate-1-oxide through diazotization-bromination, oxidation, protection and reductive dehalogenation and the yield of each step was over 90%. Then 2-mercaptobenzothiazole was used to form the unsym-azetidinone disulfide in 99% yield. Subsequently, anhydrous copper chloride, sodium azide and potassium permanganate were used separately to obtain benzhydryl 2β-azidomethylpenicillanate-1,1-dioxide in 30% overall yield. And then vinyl acetate was employed as reactant in the 1,3-dipolar cycloaddition for producing benzhydryl 2β-triazolmethylpenicillanate-1,1-dioxide in 70% yield. Finally, tazobactam was synthesized after deprotection using m-cresol and the yield was 63%. The total yield of pilot-scale was up to 8.0%.
出处
《精细化工》
EI
CAS
CSCD
北大核心
2001年第11期634-637,共4页
Fine Chemicals
基金
天津市自然科学基金资助项目 ( 0 0 36 0 1811)~~
