药物合成反应习题及答案

药物合成反应习题及答案一、举例解释下列概念：1，官能团保护；为什么保护？当分子中有多个官能团，想在某一官能团进行转换反应，为了不使其他官能团影响反应，需对这些官能团进行衍生化，这就是官能团的保护。达到反应目的后再还原这些官能团。理想保护基：试剂易得、无毒，保护基稳定，引入和脱去反应选择性好，收率高。2，相转移催化剂;一种与水相中负离子结合的两性物质，可以把亲核试剂转移到有机相进行亲核反应。相转移催化剂优点：克服溶剂化作用；不需无水操作；可用无机碱代替有机金属碱；降低反应温度。3，重排反应；重排反应是指在同一分子内，某一原子或基团从一个原子迁移至另一原子而形成新分子的反应。按反应机理可分为亲电重排、亲核重排、自由基重排和协同重排。4，合成子；合成子:组成靶分子或中间体骨架的各个单元结构的活性形式.包括：离子合成子、自由基或周环反应所需的中性分子。离子合成子：包括d合成子和a合成子d合成子:亲核性的离子合成子d---donorofelectrond合成子CNKCNCH2-CHOCH3CHOMeSHMeSRCHCRCHCHBuBuLi等价试剂a合成子：氧化性或亲电性的离子合成子a合成子：Me2C-OHMe2C=OCH2COCH3BrCH2COCH3CH2-CH-COORCH2=CH-COOR等价试剂5，协同反应协同反应：在反应过程中，若有两个或两个以上的化学键破裂和形成时，都必须相互协调地在同一步骤中完成。6,非均相催化氢化:催化剂、反应物、试剂和氢供体在两项或多项中反应，催化剂自成一相，称为非均相催化氢化。催化剂自成一相称为非均相催化剂如Pd/C为催化剂，氢气为氢供体，在反应液中还原双键的反应。1)DMAP2)DMF3)DCC4)TBAF1)AromaticElectrophilicSubstitution;芳香亲电取代2)Phase-transfercatalyst;相转移催化剂3)Carbocations;碳负离子4)trifluoroaceticanhydride.三氟乙酸酐RyojiNoyoriwasawardedtheNobelPrizein2001,Whatdidhediscover?RyojiNoyori日本名古屋大学的野伊良治因在手性催化氢化反应方面做出了突出贡献而被授予2001年Nobel化学奖。例：COOR1RNHCOR2H2(S)-BINAP-Rh+COOR1RNHCOR2SSharplesswasawardedtheNobelPrizein2001,Whatdidhediscover?Sharpless因在手性催化环氧化反应方面做出了开创性和突出贡献而被授予2001年Nobel化学奖。例：BuOOHt-BuOOHTi(OPr-i)4/(+)DETBuOOHO二、写出下列反应产物1，Cl2/NaOH/H2OHgCl2OHClOHCl+2，CCH2OAcOOHONBS/dioxaneCCH2OAcOOHOBrHOH2OC4H9CH2COOHBr2/cat.PCl3C4H9CCHOOHBr5,OHBrPh3P/Br26,NCH3OHPCl3NCH3Cl7,MeOOMeOMeBBr3CH3Br+HOOHOH8,O2NNO2NH2NaNO2/HClO2NNO2N2ClCuCl/HClO2NNO2ClHONH2HBF4/NaNO2CuClheatHOFHON2BF49,10,OOHOHOHOHHOOHPhCH2Br/K2CO3DMFOOBnOBnOBnOBnBnOOHOOHOHOHOHHOOHPhCH2Br/NaHDMFOOBnOBnOBnOBnBnOOBn11,12,OO+AlCl3O13,CHOCHOCH3CH2COCH2CH3+NaOEtOCH3CH314,CH3CH3CH2CH2OHCH3CH3H2COCH2+AlCl3215,CHOBnOBnOO(C2H5O)2P-CHCOOEt+NaHBnOBnOCOOEtE式16,NEt2+COOEt+COOEtHOheatheat17,18,CH3OClCH2COOEtNaOEtCOOEtO19,NH2ONaOBrNH220,OCH3COOOHOOH2O2/C6H5CNKHCO3/MeOHOOO21,22,H3CH3COsO4PyOHOHH3CH3C23,OCH3MCPBAOOCH324O2NCHCHNO2O2NH2CH2CNO2PhCHCHCOOEtRh(Ph3P)3ClPhH2CH2CCOOEtRh(Ph3P)3Cl25,26,NH2CH3CHON=CHCH3H2/RaneyNiNHCH2CH327MeOMeOMeOCOOEtLiAlH4MeOMeOMeOCH2OH28NO2H3CNCFe/NH4ClNH2H3CNCO2NCOOEtSnCl2/EtOHH2NCOOEtNO2NH2Zn/HClNH2NH2NO2NH2ClRaneyNiNH2NH2Cl29303132O2NOSO2CH3COOCH3H2NOSO2CH3COOCH3Pd-C/H2H3CCH3NO2LiAlH4H3CCH3NH23334BnOOBnOOBnOBnOOOBnOBnOBnHOOHOOHOHOOOHOHOHPd/CH235三、写出下列反应条件HOOHOHPhCH2BrK2CO3/DMFBnOOBnOBnHOHOCHOMe2SO4/K2CO3MeOMeOCHOacetonePd/C/H2BBr31,2,BnOOHOBnOBnOBnOBnTBSClHNNBnOOBnOBnOBnOBnOTBSBnOOBnOBnOBnOBnOTBSOHOHn-Bu4N+F-BnOOBnOBnOBnOBnOHOHOH3,4,NHOONOOBu-nNHNHOO+n-BuNH25,BnOOBnCHOBnOOBnOH6,COOHI+OHOODCC/DMAPIOOOOOHCH2COOHTsOH/C6H6OOrefluxHOHOCOOHCH3OHconcentratedH2SO4refluxHOHOCOOMe7,8,9,OHCOCl+OOOHOPhCOOHNHBocHNOOPh+NOOPhOPhNHBoc10,11,NH2Ac2O/PyNHAcBr2NHAcBrNaOHNH2Br12,ClOCO13,HOOCH3CCHH3CCOOEtPh3CNaH3CCHH3CCOCCH3CH3COOEtH3CCHH3CCOOEti-Pr2NLiH3CCHH3CCOClH3CCHH3CCOCCH3CH3COOEt14,15,OZn/BrCH2COOEtCH2COOEtOHH+COOEtLiAlH4CHOOZn/BrCH2COOEtCOOEtLiAlH4CH2OH(i-Pr-O)3AlCH2OHCH3COCH3NaOHCH3COCH316,OHOHSnCl4O17,OCH3OOCH318,NNOClH3CClPb(AcO)4AcOHNNOClH3CClOOCH3NaOCH3NNOClH3CClOH19,NNO2NOPhCH3OOHJonesNNO2NOPhCH3OCOOH20,HCrO4/H2SO4/acetoneBnOBnOCH2OHPDCBnOBnOCHO21,CH3(NH4)2Ce(NO3)6硝酸铈铵H2COOCH3CANAcOH22,CH3H2COOCH3Pb(OAc)4NaOHH2COHAcOH23,CH3OMEMH3COH3COOMEMCH3CH3SeO2CH2OHOMEMH3COH3COOMEMCH3CH3+CHOOMEMH3COH3COOMEMCH3CH3E24,HOOHPb(OAc)4OO25,PhCOOHOZn-Hg/HClPhCOOH26ClCOCH2ClClClCHCH2ClClOHNaBH427CHCHCHOAl(C2H5O)3CHCHCH2OHCH3COCH3Al(OPr-i)3i-PrOHCHH3CCH3+H3CCH3OOH2829四、写出系列反应机理或历程1，LiAlH4还原酯机理2，OHH3COHH3Ct-BuOCl/CHCl350CClCH3CH2ClOH2CCHCCH3OONaOH+OOONaNH2H2OOOOH-H2OO2,CHOCHO+CH3NH2OCOOHCOOH+OCOOHCOOHNCH3H+heatONCH3颠茄酮NaOH3,NOHH2SO4NHO4,H3CCH3OCH3H3CCH3OHCH35,五、用简单化合物为原料（或给出的化合物为原料）合成下列目的物BrCH3BrNMeONH2NMeONHH3CNH2+1,2,FOClNH2ClBrCH2COBrNHCOCH2BrClZnCl2NHCOCH2BrClOFNH2OClClClCH2COClHNOClClCOCH2Cl(CH2)N4NHNOClCl3，CH3COClAlCl3CH3OClCH2COOEtNaOEtCOOEtONaOHheatOHClO-OHAgNO3COOHCH2OBrCOOHNaOH4,ClOCH2N2CHN2OAg2OH2OHCCOH2OCOOH5,6,HOHOHOCOOHBnOBnOBnOCH2OH