7-氨基-3-乙烯基头孢烷酸合成和研究.pdf

武汉工程大学硕士学位论文7-氨基-3-乙烯基头孢烷酸的合成研究姓名:邓伏礼申请学位级别:硕士专业:化学工艺指导教师:()fixime)禾1]头孢地尼(Cefdinir)的重要中间体。作者以青霉素G钾盐为原料,经酯化、氧化、扩环、还原、Witting反应、(7-AVCA),总收率22%。反应历程:①(PEGS)的合成:青霉素G/,反应温度40--45℃,反应时间3h;以自制过氧乙酸为氧化剂,反应温度5~10℃,反应时间2h,收率90%。②(CAG)的合成:、用氧化钙作缚酸剂,在108℃,以四氯化锡为催化剂室温反应16h闭环,收率60%。③(CADO)的合成:、99碘化钾、45mlDMF,,于室温反应15min,收率90%。④7一苯乙酰氨基一3一环外亚甲基头孢烷酸对硝基苄酯(CADO)通过碘代,Witting反应引入乙烯基,),收率66%。⑤(),用锌粉在酸性条件下将硝基还原为氨基,(7-AVCA),收率72%。关键词青霉素G中间体7-AVCA合成武汉工程大学硕士学位论文IIAbstractAbstract7-amino·-3—-vinylcephalosforanicAcid(7--AVCA)-AVCAwassynthesizedbyesterificatingpenicillinGpotassiumsalt,oxidating,aring—expanding,reducing、WittingreactingandspliUing,thetotalyeildwas22%.Theprocedureisfollowing:①Tllepreparationofp-nitrobenzyl6-phenylacetamido·2,2一dimethylpena-m-3一carboxylate-l-oxide(PGES):penicillinGpotassiumsaltwasreactedwithp-nitrobenzylbromidetoproducethe4·nitrobenzylesterofpenicillinGacid,reactiontime3h,weightratioofPGKandpNBB=,thetemperature40-45。C;theesterwasoxidizedwithperoxyaceticacid,reactiontime2h,thetemperature5~1O℃.TheyeildofPGESwas90%.(9Thepreparationofp-nitrobenzyl7-phenylacetamido一3-exomethylenecepham-4一carboxylate-1-oxide(CAG):PGESwasreactedwithN—chlorophthalimideatthetemperature108℃,calciumoxideastheacidscavenger,;Withoutseparation,CAGwasformedinacyclizationreactionofthering-poundwithSnCl4,%.③ThesynthesiseofP—nitrobenzyl7-phenylacetamido--3·-exomethylenece·-pham·-4·-carboxylate(CADO):,Ⅺ99,45mlDMF,,temperature25℃,%.④P-nitrobenzyl7-phenylacetamido一3一exomethyle-necepham-4一carboxylateWasreactedwith12,thenusedWittingreactiontogainP··nitrobenzyl7-phenylaceta