第二章 烷基化反应VIP免费

第二章烷基化反应(AlkylationReaction)C-O键的形成C-N键的形成C-C键的形成第一节氧原子上的烷基化反应（醇和酚的烷基化）一、醇的O-烷基化OHCat.H2SO4heatO简单醚或对称醚的制备1.卤代烃为烃化剂混合醚常用制备方法ROH+R'XROR'BaseWilliamsionReactionNaI，KI，促进反应加速RI>RBr>RCIClO2NEtOH/NaOHheatOEtO2N95%非拉西丁中间体苯拉海明PhCHPhBr+Me2NONa+HCl.Me2NCl¶þ¼×±½heatNaOH/¶þ¼×±½heatCHONMe2PhCHPhOH差向异构50¡æ,1hOHCH3I/NaH/THFOCH3CH3(100%)ciscisCH350¡æ,1hOHCH3CH3I/NaH/THFOCH3CH3(100%)transtrans多卤代物的醚化CHCl3+3CH3ONaCH(OCH3)3CCl4+4CH3ONaC(OCH3)4OHBrNaOHO分子内醚化，制备环氧2.磺酸酯为烃化剂对甲苯磺酸酯，甲磺酸酯，三氟甲磺酸酯CHOHCH2OHCH2OHMe2CO/HClCH-OCH2OHCH2-OC(CH3)2C18H37OTs/KOH/Tol>110¡æ,3hCH-OCH2OC18H37CH2-OC(CH3)2EtOH/HCl,2hCHOHCH2OC18H37CH2OH3.环氧乙烷为烃化剂酸碱下的不同位点，易聚合Ph-CH-CH2O+MeOHPh-CH-CH-OHPh-CH-CH-OMe+OMeOHH2SO4,5h(90%)(10%)Ph-CH-CH2O+MeOHPh-CH-CH-OMePh-CH-CH-OH+OHOMeCH3ONa,5h(25%)(75%)4.烯烃为烃化剂CNCH3ONaCNH3COOHHHO+H3PO4BF3-20oC-0oCOHHO叔丁基醚制备5.氟硼酸三烷基傟盐为烃化剂OHBrOOHBrOHNH2ONaNO2/HBrH2OL-valineOMeBr(CH3)3O+BF4-r.t.NHBocOHPhCH2BrNHBocOOHNOCase：二、酚的O-烷基化1.卤代烃为烃化剂80~100¡æ,19.6x10exp4PaCONH2OHEtBr/NaOHCONH2OEtOHCH3I/K2CO3/acetoneheatOCH3低沸点卤代烃OH+BrNaH/THFrefluxOBnOHClCH2OCH3+NaH/THFr.t.OMOMNaHOOOHH1eqCH3I/NaOHOOOCH3HOOMeHOOOH1eqCH3I/NaOHOOMeMeOOOH分子内氢键的影响2.硫酸二甲酯为烃化剂CHOOHOCH3Me2SO4/NaOHCHOOCH3OCH33.重氮甲烷为烃化剂H2CN+NHORH3CNNCH3ORO+-N2R=ArorR'-C-_OROMeCOOMeOMeExcessiveCH2N2OHOHCOOH2molCH2N2OMeCOOMeOH4.缩合试剂（DCC，偶氮二羧酸酯）CNNHORHCHNNHORHOArNHCONH+ArOR100¡æPhOH+PhCH2OHDCCPhOCH2PhOH+ROHPPh3/EtOOCN=NCOOEtOREtOOCN=NCOOEtPPh3NCOOEtCOOEtPh3PN+-ArOHROHEtOOCNHNHCOOEtPh3POR+ArO-ArORPh3PO+第二节氮原子上的烷基化反应一.氨及脂肪胺的N-烷基化反应RX+NH3RNH3+X-BaseRNH2RNH3+X-+NH3RNH2+NH4+X-RNH2+RXR2NHR2NH+RXR3N跟卤代烃的反应是主要方法之一，缺点：易得到混合胺（一）氨及胺和卤代烃的反应1.伯氨的常用制备方法OHOBrNH3(70mol)70%OHONH2(1):氨水和卤代烃的反应用大大过量的氨水，抑制进一步反应，该方法在工业中应用广泛NO2O2NClNH3/AcONH4170oC,6hNO2O2NNH2制备芳香胺(2):Gabriel反应应用范围较广，除少数活性较差的卤应用范围较广，除少数活性较差的卤代芳烃之外，适于各种带伯卤代烃的代芳烃之外，适于各种带伯卤代烃的取代基取代基NHOOKOH/EtOHN-K+OORX/DMFNOORNH2NH2HCl/H2O180oCNHNHOO+RNH2COOHCOOH+RNH2NMeONHNH2¿¹Å±Ò©²®°·àPrimaquineNMeONHNOONMeONH2NOOBr+NHOOBrBr+(3):Délépine反应(乌洛托品）NNNNRXN+NNNRX-HCl/EtOHRNH2NNNN+COCH2BrO2NN+NNNC6H5Cl33~38oC,1hCH2CONO2C2H5OH,HCl33~35oC,1hCOCH2NH2.HClO2N氯霉素中间体反应条件温和，思考：该中间体能否用Gabriel反应做？(4):三氟甲磺酰胺法(CF3SO2)2O+PhCH2NH2Et3N/CH2Cl2-78oCPh2CH2NHSO2CF3Ph2CH2NHSO2CF3n-C7H15Br/NaOHPh2CH2NHSO2CF3C7H15-nNaH/DMFPhCH=NC7H15-n10%HCl/THFheat/3h80%n-C7H15NH22.仲氨，叔胺的常用制备方法(1):直接卤代烃的反应BrMeNH2/EtOH110oC,18hNHMe78%NMetrace+NO2ClCl40%aqMeNH2DMSO,25-35oCNO2NHMeCl适用范围：a:位阻较大的卤代烃b:活性较低芳香胺的制备叔胺的制备CH2NHCH3HCCCH2ClCH2NCH3HN+n-BuBrLiÝÁNBu-n(2):酰胺间接法a:三氟甲磺酰胺法(CF3SO2)2ORNH2RNHSO2CF3R'X/NaOHRNSO2CF3R'LiAlH4RNHR'b:膦酰胺法(EtO)2POH/CC4RNH2R'X/NaOHRNHPO(OEt)2RNPO(OEt)2R'HClRR'NHc:苯磺酰胺法（Hinsberg)反应ArSO2Cl/NaOHRNH2R'X/NaOHRNHSO2ArRNPSO2ArR'Ëá»ò¼î/H2ORR'NHONONO2H2NOONONO2NHO1.TFAA,CH2Cl22.TBACl,Me2SO410%NaOHd:三氟乙酰胺法e:鏻鎓盐法RNH2+R'OP+PPh3DMFRR'NH+PPh3POR'R''NH2+ROP+PPh3DMFRR'R''N+PPh3PO（二）...