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第七章还原反应Chapter7ReductionReaction第一节不饱和烃的还原一炔、烯的还原1多相催化氢化常用的氧化cat有：Ni(骨架)、Pd、Pt、载体Pd/C及Pt/C。Pd/CaCO3/H2/喹啉1kg/cm2,30-370COHCH2OH(78%)OHCH2OH(维生素A中间体)喹啉为抑制剂，可使C=C而不进一步还原a：毒剂(Poisons)和抑制剂(Inhibitors)CC(1)影响氢化反应速度和选择性的因素RaneyNi/H2100kg/cm2O250C1200C2600COOHOHb:反应温度和压力c:溶剂的影响溶剂:EtOH53%47%EtOH/HCl/H2O93%7%EtOH/KOH35-50%65-50%(2)炔、烯的选择性加氢及立体化学(避孕药双炔失磺酯中间体)(位阻小的一面加氢)Ni2B(P-2)/H2Ph(95%)CCCH3H2N-CH2CH2-NH2CCCH3HHNiBH4/NaOHaq,EtOH/250C+Ni(OCOCH3)2Ni2BH2(乙醇中制备P-2型，水中制备P-1型)(98%)Ni2B(P-2)/H2CHCH2EtOHCH2CH3RaneyNi/H2RRHHPd/CaCO3/H2/DMF/喹啉硫2kg/cm2,50-550COHOHOHOHCONH2ClN(CH3)2OOOCH2(58%)OHOHOHOHCONH2N(CH3)2OOOHCH3顺式加氢+Pd-C/EtOH5h△(65%)OCH3CH3CHOOCOOCH3CH3CHOOCO(3)转移氢化(安宫黄体酮)++HCCHHHHNNHCCNNCCNNPhPhCu2+空气PhPh(80%)CCCH2CH2NH2NH2(69%)CHCH3CH2(CH2)8COOHK3Fe(CN)6(CH2)9NH2NH2COOH用肼或二酰亚胺还原(C=C取代基增多，氢化明显下降)(93%)△CH2CHCH2SSCHCH2CH2C7H7SO2NHNH2C3H7SSC3H7(用其他方法还原多导致二硫键断裂)(90%)(Ph3P)3RhCl/H2/PhHOHOH选择性还原末端及环外双键2均相催化氢化(94%)(Ph3P)3RhCl/H2OCH3H2CCCH3OCH3CHCH3CH3+δδHCCBH3BH2CCCCBH2H+3H2O2/NaOH（醇）BCCHH3OH2OOHB(OH)3CCHHBCCH(饱和烃)3硼氢化反应注:(1)BH3n-BuCH=CH2an-BuCH2CH2BH2n-BuCH=CH2bn-BuCH=CH2c(n-BuCH2CH2)2BH(n-BuCH2CH2)3B反应速度:abc2+XCHCH2BH3XCHCH2CH2BCH3XB(2)X=-OCH391%9%当X为供电子基时，更有利单硼化物生成i-PrMei-Pri-Pr+CHCCHHBH3CH2CH3BCHCH2CH3BMeMe2CHCH2BH57%43%95%5%当烯烃碳原子上取代基数目相等时，取代基的位阻对反应结果影响较大。3n-C8H17H2O2/NaOH(95%)3n-C8H17CH2CH2CHCH2BH3H2OOH250C22B3H6/Et2OCrO3/H3O/EtOH(78%)OCH3BH250CCH3CH3(3)利用上述性质可制备醇或酮PtO2/H2/AcOH3kg/cm2,250C(100%)COOHCH2CH2COOH90kg/cm2,250CPtO2/H2/EtOHPh(60%)COHCOOHCOHCOOH二芳烃的还原1催化氢化还原(抗胆碱药安胃灵中间体)Na/NH3/EtOH(95%)COOHCOOHLi/NH3/EtOH(88%)CH3CH3供电子基双键在2，5位形成吸电子基双键在1，4位形成且吸电子基有利于还原，故为C离子历程。2化学还原法++e(Na)e(Na)HHHHNH3HHNH3HHHHHH环上有给电子取代基时，反应速率减慢。环上有吸电子取代基时，反应速率加快。Li/NH3/EtO(50%)-400COHHCH3OHOCH3OHCOCH2NH2NCCH2第二节醛酮的还原反应一还原成烃的反应1Clemmensen反应(Zn+HgCl25-10%)PhZn-Hg/HCl/Tol(90%)Ph△(CH2)2COOH(CH2)3COOHOCCOOEtZn-Hg/HClCOOEt△CH3OHCHOCCH3COOEtCOOEtZn-Hg/HCl△CH3CH3OCCH2CH2CH2(1)-酮酸及其酯还原成-OH，、-酮酸及其酯类还原成CH2αβγPhPhZn-Hg/HClCH3CH3OCCHCHCH2CH2CH2COOEtPhPhZn-Hg/HClCOOEtCHCHCH2CH2(2)孤立双键不受影响，与共轭双键被还原COZn/HCl/Et2O0-50C(84%)OHHR'EtONaorKOHR'R'+RH2NNH2N2CORCNNH2RCH22Wolff-（Kishner）-黄鸣龙还原注：(1)黄鸣龙改进:加二聚醇乙二醇(DEG)或三聚乙二醇(TEG)将生成的水带出，使收率提高许多。CHOCH3CH3CH380%H2NNH2H2O/KOHCH3CH3CH3CH3CH2CH3CH3CH3(80%)85%H2NNH2H2O/KOH/TEG180-2000CCH3HOCOCH3HOCH2(85%)(95%)PhPhDMSOPhPh+CPh2t-BuOKCOH2NNH2NNH2CH2N2(2)对高温或强碱敏感的基团，不能采用上述方法。先转变成腙，再还原。KBH4/CH3OH250C,5h(86%)CH2CHOCClBrCH2ClBrOH二还原成醇的反应1金属氢化物还原剂(邻氯喘息定中间体)KBH4/EtOHCCHOHOOHCCHOH(避孕药炔诺酮中间体)△NaBH4/EtOHOOHOO(酮的反应活性大于、-不饱和醛、酮)αβ(1)9-BBN/THF,00C(2)H2NCH2CH2OH(95%)OCH3COOC2H5CH3COOC2H5OH9-BBN：9-硼双环[3，3，1]壬烷，可迅速还原、-不饱和醛、酮，而不影响分子中其他易还原基因αβ反应机理：RR'CO+NaBH4(H-)RR'CHOBH3NaR''OHRR'CHOH+NaBH3OR''其他氢化物，如：LiAlH4与之机理相同-HOPr-ii-ProC1C2Al(OPr-i)3C1C2i-ProOCH2PNO2NHAcAlHOHC6H4OCH2PNO2NHAcHC6H4O2醇铝还原剂(Meerwein-Ponndorf-Verley反应)C1C2C1C2CH2OHPNO2NHAcHC6H4HOHCH2OHPNO2NHAcHC6H4HOHi-ProC1C2-Me2C=Oi-ProC1C2COAlCH2PNO2NHAcHC6H4OOMe2HOAlCH2PNO2NHAcHC6H4OHH2ORaney-Ni/EtOH5kg/cm2,r,tOCH2OAcAcOOAcCHOOOAcCH2OHOAcOOAcCH2OOAcOAc(92%)(天麻素中间体)3催化氢化还原•金属+NH3(l):一般溶解金属还原；对炔烃还原为反式烯•金属+NH3(l)+质子溶剂：Birch还原•金属+醇：Blancreduction、PinacolCoupling4溶解金属还原PinacolCouplingBlancReduction•溶解金属还原的一般过程：双电子化，双质子化。MeOMeOMeOMeOMeOMeOH2/Pd-BaSO4/Tol喹啉—硫(84%)ClCOCHO(63%)NO2ClCOO2NLiAlH[OC(CH3)3]3NO2O2NCHO第三节羧酸及其衍生物的还原一酰卤的还原NaBH4/AlCl3(84%)NO2CH2OHCOORO(CH2CH2OCH3)2NO2NaBH4/RCONHPh1000C,5h(89%)CH2OHCOOCH3NCNCH3NC二酯和酰胺的还原1还原成醛Rosenmund还原COOEtNa/EtOH/AcOEt85-900C,1-2h(78%)CH2CH2CHCH2CHOHBouveault-Blanc反应COOEtNa/EtOH△CH3NCHCH2CH3CH3CH3NCHCH2CH3CH3CH2OH(心血管药物乳酸心可定中间体)COOC4H9-nAlH(i-C4H9)2(86%)COOC4H9-nCHOCHO2还原成醛(86%)LiAlH2(OC2H5)2ClCON(CH3)2ClCHOMeO(1)Na/Liq/NH3/Et2O(2)H3OMeOHCH2COOCH3COOCH3OHO(96%)(1)Na/二甲苯(2)HOAcCOOEtCOOEtCHO(CH2)321400C(CH2)32COH3双分子酯还原成偶姻PhLiAH4/THF△Ph(80%)CH3NCH2NHCHCOCH2CH3NCH2CHCH2NHCH2CH3CH3PhPhLiAH4/Et2O/HCl4hPhPh△HOCH2CCOCH3CH3NHOCH2CCH2CH3CH3NHCl(氯苯达诺)(地恩丙胺中间体)4酰胺还原成胺COOMeH2/Raney-Ni/CH3OHNH31kg/cm2,250CCOOMeNCH2NCH2H2/5%Pd-C/H2O-HCl1.5kg/cm2,25-300C(70%)CH3NHCH2CH2ClCNOH3CO2NCH3NCH2OH3CH2NNH2三腈的还原(凝血酸中间体)(VB6中间体)B2H6/THFCNNO2250CNO2CH2NH2KBH4/PdCl2/MeOHr.t.(90%)CH2NH2CN(不影响-NO2)LiAlH4/Et2O(93%)COOH(CH3)3CH2OHC(CH3)3C四羧酸及酸酐的还原NaBH4/AlCl3(82%)O2NCOOHO2NCH2OH(加AlCl3起催化剂作用，否则不还原)B2H6/THF(92%)COOHIICH2OH(94%)20-250C,2hB2H6/THF2O2NCOOHCH2O2NCH2CH2OHCOOEtCOOEt(88%)-180C,10hB2H6/THFHOOOHO(CH2)4(CH2)4CH2(B2H6可还原COOH-CH2OH，对其他官能团无影响)(60%)LiAlH4/(n-C4H9)2OOOOCH2OHCH2OHNaBH4/THF250C,1h(97%)(成内酯)OOOZn-HOAcOOOO[电解](91%)COOHCH2OHHg(100%)CH2(CH3)2NNPb[H](CH3)2CO(96%)CH2Pb[H]NH2CNPb/Pb-15%H2SO410A,27.5V,300C(78%)COOHOHNH2NH2CH2电解还原Fe/H2O/HCl3h(93%)△ClCH3NH2NO2ClCH3(双氯咪唑青霉素钠中间体)第四节硝基化合物的还原一活泼金属还原剂1Fe还原剂(70%)Fe/HCl/FeCl31h△CH3CONO2NH2CH3CHCH3COCH3CH(60-70%)10-150C,30minFe/H2O/HClONH2NNOOONO(甲氧非那明中间体)(痢特灵中间体)(不影响其他不饱和官能团)MeOZn/HCl/EtOH-H2O80-850C,3hMeO(70%)CH2CH2NH2HONO2CH2CH2HOHCl2其他金属还原剂Sn/HCl(65%)CH3CH3O2NCH3N(CH3)2800CHClH2NCNCH3NCN(多巴胺中间体)(驱虫药甲胺苯脒中间体)EtONa2S2/H2O138-1400C,12h(95.5%)EtONH2NO2二含硫化合物为还原剂Na2S2/NH4Cl80-850C(61%)O2NHONO2HONO2H2N(只还原一个-NO2，而保留另一个-NO2)Na2S2O4/H2O30-400C,30minOONH2NO2COONaNHHNOOCOONaNHHN(84.5%)HClNH2OONHHNCOOHH2/Pd-CaCO340-450C,2kg/cm2(98%)CHOHCH2OHO2NCNHCH