第三期-顾振华

谈谈实验室安全和实验的个人体会导师：麻生明研究员汇报人：顾振华有机所枫林论坛往者可谏来者可追2主要内容实验室安全个人的实验科学的信誉问题GivingProperCredit3溶剂(1)对神经系统破坏：抑制神经系统的传导冲动功能，产生麻醉，神经系统障碍或引起神经炎等。酒精、苯、氯化乙醇、二氯乙烷、汽油、甲酸戊酯、醋酸戊酯、二甲苯、三氯乙烯、丁醇、松节油、煤油、丙酮、三氯甲烷、异丙苯等。(2)对肝脏机能损伤：损伤肝脏机能，引起恶心、呕吐、发烧、黄疸炎及中毒性肝炎；一般氯化烃类均会引起肝脏中毒现象。四氯化碳、氯仿、三氯乙烯、四氯乙烷、苯及其衍生物等。(3)对肾脏机能破坏：肾脏为毒物排泄器官，故最易中毒，且因血氧量减少，亦足以使肾脏受害，发生肾炎及肾病。烃类之卤化物、苯及其衍生物、二元醇及其单醚类、四氯化碳、乙醇等。(4)对造血系统破坏：破坏骨髓造成贫血现象。苯及其衍生物(硝基苯)如甲苯、氯化苯、二元醇等。(5)对粘膜及皮肤刺激：刺激粘膜，使鼻粘膜出血，喉头发炎，嗅觉丧失或因皮肤敏感产生红肿、发痒、红斑及坏疽病等。三氯甲烷、醚、苯、丙酮、甲醇、石油、氯酚、二氯乙烯、四氯化碳等。4控温仪毛细管温度计、温度计套管核磁管高温高压反应5操作规范整洁、有章程（洗瓶、药品的存放(苯胺)，称量、取用(双层手套法、注射器的正确使用)、了解不同试剂的性质(液氨)）过柱溶剂的转移,溶剂球的固定,防护镜不要“意气用事”试管,蒸馏“空中接力”6多借鉴别人的经验LiAlH4：Workupbestconductedby“1,2,3-method”for1.0gLiAlH4used,added1mLH2O(slowly)then2mLof10%aqueousNaOH,then3mLofH2O无故乱翻书8:2规则7全合成：广度方法学：深度2.Corey-Bakshi-ShibatareductionCorey-Chaykovsky-epoxidation(Corey-ylide)Corey-FuchsreactionCorey-KimoxidationCorey-WinterolefinSynthesis3.CouplingReactionJohnF.Hartwig根深则叶茂1.PhilBaranChemical&EngineeringNews,2007,85,38OneofthethingsIthinkPhilisreallygoodatishavingasenseofwhatisnew,whatisnovel,andwhatneedstobediscoveredinourfield,remarksgraduatestudentNoahZ.Burns.It'snotaneasythingtodoinamaturefield.“……make(+)-ambiguineHin10stepswithoutrelyingonanyprotectinggroups(Nature2007,446,404)……Baranhasareputationasawunderkind……8TheNobelPrizeinChemistry1913inrecognitionofhisworkonthelinkageofatomsinmoleculesbywhichhehasthrownnewlightonearlierinvestigationsandopenedupnewfieldsofresearchespeciallyininorganicchemistryAlfredWerner1866-19199KarlZieglerFederalRepublicofGermany1898-19731953年他利用铝有机化合物成功地在常温常压下催化乙烯聚合GiulioNattaInstituteofTechnologyMilan,Italy1903-19791954年在德国化学家K.Ziegler乙烯低压聚合制成聚乙烯重大发现的基础上，发现以钛和烷基铝为催化剂，丙烯在低压下高收率地聚合，生成分子结构高度规整的立体定向聚合物──聚丙烯，具有高强度和高熔点，开创了立体定向聚合的崭新领域。TheNobelPrizeinChemistry1963fortheirdiscoveriesinthefieldofthechemistryandtechnologyofhighpolymers10Org.Syn.2000,77,141……themixtureisheatedto85oC(internaltemperature)over30minbymeansofanoilbath,……实验操作：胆大、心细、脸皮厚因为了解，所以失败11假设设计反应实施yesno基于呋喃酮骨架的周环反应研究12CO2Me+110COOHHPhBF3·Et2O,Cl3CMe5mol%Pd(OAc)2OOPhMeO2C4c45%,111cOOPhMeO2CMeO2C12%,112c(?)13COOHPhHCO2Me(110)Pd(OAc)2,additiveOOEPhOOEPhE4c111c113cOOPhH+114cE=COOMeCCl3Me,35oCOOEPh115cEEAdditive--100mol%BF3·Et2O100mol%BF3·Et2O10628--4040152810mol%BF3·Et2O27643Entry1b235c111c113c114ctime/h12122412100mol%Sc(OTf)33375161810mol%Sc(OTf)3352028712d47114812yield(%)a110(equiv)1.01.01.01.03.03.05.0115c--------5----100mol%BF3·Et2O2228204148.03aYieldsweredeterminedby1HNMRanalysiswithCH2Br2astheinternalstandard.b14%yieldof4cremainedasdeterminedby1HNMRanalysis.cPdCl2wasusedasthecatalyst,67%of4cremainedasdeterminedby1HNMRanalysis.d30mol%Sc(OTf)3and4.0equivofBF3·Et2Owereused.14A.K.Ghosh,J.Cappiello,D.Shin,TetrahedronLett.1998,39,4651OOOOOOMeGrubbsCat.OOOOMeORuGrubbsCat.Ti(OiPr)4OOOOMeOOOOOOMeORu(VI)Ti15COOHHPhConditions4cMeOOPhMeO2C113cMeO2CHHHHHHHHThemechanismstudyOOPhMeO2C112cMeO2CWheredoesthetwohydrogen(inred)of4cgo?Wheredoesthethreehydrogen(inblue)of113ccome?Is112caprecursorof113c?16OOEPhE113cOOEPhE112cHaHcHbHdCDCl325oCThe1HNMR(300MHz)spectraofthemixtureof112cand113cinCDCl3at25oC.(a)1HNMRspectrumofthemixtureobtainedrightafterisolation;(b)The1HNMRspectrumafter4hours;(c)The1HNMRspectrumafter6hours;(d)The1HNMRspectrumafter27hours17HHR2EEOOR1OOR1R2EEH1,7-Hshift1,7-HshiftOOR2ER1EOOR2ER1E18PathA78OOR3R2R1OOR3R1R22+2cycloaddtionOOR3R2R11,5-HshiftOOR3R2R1electrocyclicrearrangement45Int22Int23HHPathB4578Int24OOR3R2R1OOR3R1R21,5-Hshift8-electro-cyclizationOOR3R2R1HxyleneOR3R4O100oC,6hOOR2R3R4R1R2R119HHOHHOHHOHHO+Oxylene83a84aa84ab81%1:1.380oC,3hOInt25Diels-AlderReactionOOOBr+ROOROXR(a)Ph3PBr2,CH2Cl2,Et3N(b)Ph3PI2,CH3CN,Et3N(c)(TfO)2O,CH2Cl2,PyZnBrPd(0)R2083aOX=O,86aX=NEt,86bX=NPh,86c+XOOxylene,55oCHHHXOOHO8786X=O,49%,87aaX=NEt,77%,87abX=NPh,91%,87ac21RRIncreasingthesterichindranceXHHOHHOHHOHHO+O84aa84abInt25O?OD-A-electrorearrangement22OxyleneR=Me,83b90oC,2hORR56%,90bOn-BuR=n-Bu,83cR=Ph,83d57%,90c;8%,91c77%,90d91c23O90bO91bNEtOOxylene,55oCHMeHEtNOOHO87bb86b+24h,53%aa28%of90bwasrecovered86bDiels-AlderReaction2445vfOOREtEtH7%,Z-94vfOOREtEt29%,E-94vfOOR+EtEtxylenereflux,6h+OtherunidentifiedproductsInt26aOOREtEtH1,7-Hshift1,5-HshiftR=-NaphthylOOREtEtHInt26b2545fc,R1=Me45ff,R1=EtOOPhR1R1OOPhxylenerefluxa10%of45ffwasrecovered3.5h,67%,E-94fc6h,64%,E-94ffaOOPhR1R1R1R1H26ORTEPrepresentationoftrans-96scOOPhOOPhxylenesealed,200oC5hOOPh70%,trans/cis=1.9:145sc96sc27R345OOR3R2R11,5-HshiftOOR3R2R1OOR3R2R1R4R4R4Int24OOR3R2R1R4HHInt28OOR3R2R1R4HH1,5-HshiftHOORLUMO*HOMOROOHLUMO*HOMOR=CH=CH2R=CH=CH2(H)(H)R4R2R1R2R1R3R428OOH3CH3CPhDDDDDxylene,110oC6h,64%OOPhH3CCH3DDDDD45gc-d578gc-d54897%98%D97%D97%D98%D84%D93%D563%D2913c-d6-d44c-d6-d45gc-d644c-d6MgBra-bOHCD3D3C(D)/HcOCO2MeCD3D3C(D)/HeOOPhD3CD3CHdOCO2MeCD3D3CHConditions:(a)C2H5Br,Mg,THF,thenacetylene;(b)CD3COCD3,34%;(c)NaH,Et2O,thenClCO2Me,71%;(d)n-BuLi,Et2O,-78oC;thenH2O,-78oC,38%;(d)2-allyl-4-phenylbuta-2,3-dienoicacid,Pd(OAc)2/TFP,K2CO3,DMSO,54%,95%D.30OOPhD3CD3C45gc-d695%Dxylene,110oC6h,84%OD3CCD3OPh85%D78