1、C=ORR(H)R被G取代C=OGR(H)COGRG=XO-C-ROORNH2 (NHR,NR2)R-C=N-H2O酰卤酸酐酯酰胺腈 R-C-GONu-R-C-GONu-G-R-C-NuOn注意能够生成注意能够生成酮酮的反应的反应A.RLi和和RMgX OR-C-XR-CR-COOO或RMgXOR-C-R通过降低温度来控制反应停留在生成酮这一步。OCH3-C-ClCH3CH2CH2CH2MgCl(C2H5)2O/FeCl3-700CO72%CH3CH2CH2CH2MgCl(C2H5)2O/FeCl3室温OCH3-C-ClOHOClCH3MgI-150COCH3CH3CH3OR-C-OR2 RM
2、gXH3+OOHR-C-RRORO-C-OR3 RMgXH3+OOHR-C-RROH-C-OR2 RMgXH3+OOHR-CH-RSNOSOMgBr21.2.H3+OOHSNSBrOCH3MgOMgBrOCH3NCOOCH3CH3OOCNOHHOCH3OCH3OOCH3OCH3OHC-OC2H51.2 C4H9MgBr2.H3+OOHOC2H5O-C-OC2H51.3 C2H5MgBr2.H3+O(C2H5)3COH2.H3+OOOOO1.2 CH3LiOOOHH3+OOHO1.CH3Li2.H3+OC-COOC2H5CH3CH3C CCH3CH3CH3O70%R-C-NH2ORMgXR-C-
3、NHMgXO-RHRMgXR-C-NHMgXOMgXRH3+OR-C-ROR-C NRMgXR-C NMgXRH3+OR-C-ROCH3-C-CH2-C-NH2CH3CH3O1.2 C6H5MgBr2.H3+OCH3-C-CH2-C-C6H5CH3CH3O1.C6H5MgBr2.H3+OOCH2CNCH2-C-CH3-C-CH2-C-ClCH3OCH3-C=CH2CH32CuLi+-50CCH3-C-CH2-C-CH2=C-CH3CH3OCH3C2H5O-C-(CH2)8-C-ClOO(C2H5)2CdC2H5O-C-(CH2)8-C-C2H5OOR-C-NH2OR-C-OHO2 RMgX(2
4、 RLi)2 RLiR-C NR-C-ClOR-C-XOR-C-HORMgX(RLi)R2CuLiR2CdRCORCH3-C-ClOH2OCH3-C-OHO+HCl(CH3CO)2OH2OCH3-C-OHO2R-C-OC2H5OH2OR-C-OHO+C2H5OHNaOH 250CR=相对速率CH3 ClCH2 Cl2CH CH3CO Cl3C 1 290 6130 7200 23150吸电子基团对酯的水解有利CH3-C-OROH2OCH3-C-OHO+ROHHCl 250CR=相对速率 CH3 C2H5 (CH3)2CH (CH3)3C C6H5 1 0.97 0.53 1.15 0.69空间
5、阻碍小对酯的水解有利 R-C-OROH+R-C-OROHH2OR-C-OROHOH2R-C OROHOHH-ROHR-C-OHOH-H+R-C-OHOOH-R-C-OROR-C-OROOH+ROR-C-OHO强碱弱酸酸碱中和+ROHR-C-OO H2ONaOHCH3-C-OC2H5OCH3-C-ONaO+C2H5OHCH2OOCC17H35CH2OOCC17H35CH-OOCC17H35NaOHCH2OHCH2OHCH-OHC17H35C-ONaO3+HOCH2CCOOCH2CCH2OHCH3CH3CH3CH3羟基特戊酸新戊二醇单酯SOCl2ClCH2CCOOCH2CCH2ClCH3CH3CH
6、3CH3HNO3酸性条件下酯水解ClCH2CCOOHCH3CH3CH3CH3HOCH2CCH2Cl+生成的3-氯-2,2-二甲基丙醇被HNO3氧化成3-氯-2,2-二甲基丙酸,从而推移平衡,使反应进行到底。HNO3R-C-NH2OR-C-NHROR-C-NR2OH2OH+或OH-R-C-OHO+NH3RNH2 R2NHC-CH3OH3+O乙酰苯胺NH-CH3C-OHONH2+苯乙酰胺CH2C-NH2OH3+OCH2C-OH +NH3O R-C=NH+R-C=NHH2OR-C=NHOH2-H+R-C=NHOHR-C-NH2OR-C-OHOH3+OR-C=NOH-R-C=NOH-OH-R-C=NH
7、OHH2OR-C-NH2OR-C-OOH2OOH-R-C-GOROHH+或OH-R-C-ORO+HGCH3-C-ClOCH3-C-OHCH3CH3+CH3-C-OO-C-CH3CH3CH3N(CH3)2NH(CH3)2Cl6368%+ONOOONCNCCNCNONOOOHOOCHOOCCOOHCOOHC2H5OH/H2OKOH回流 5 天C-ClO+HONH3C-OO+NH4ClHO(CH3CO)2OCH3COOOOOC2H5OHBF3 (C2H5)2O,室温SOCl2OClOOOOOn-C4H9OHCOOHOC4H9On-C4H9OHH2SO4OC4H9OOOC4H9ROHH+R-C-ORO
8、+ROHR-C-ORO低沸点醇高沸点醇CH3OCHOCH2CH2OHOCOCH3O+Zn(OAc)2Sb2S3COCH2CH2OOCOn涤纶CH2OHCH2OHCH3OHKOHCH2OOCCH3CH2OOCCH3+CH3COOCH3OCH3OCH3OOAcH2O2,NaHSO4CH3OH,室温OOCH3OCH3OOAcHOOCH3OCH3OAcCH2=CH-C-NH2O+C2H5OHOH-CH2=CH-C-OC2H5O+NH3C-NHCH3OCH3OHH+C-OCH3O+CH3NH2R-C=NH+R-C=NHROHR-C=NHHORR-C=NH2ORH3+OR-C-OROR-C=NROR-C=
9、NORR-C=NHORROH-RO-H2OR-C-OROOH-C-HOHCNCHCNOHC2H5OHH+CHCOOC2H5OHBrCH2CH2CH2CH2Br2 NaCNNC(CH2)4CNC2H5OHH+C2H5OOC(CH2)4COOC2H5R-C-OROR-C-OHO+ROHH+直接酯化R-C-XO(RCO)2O+ROHR-C-ORO亲核加成-消除R-C-NH2ORCN+ROHH+或OH-R-C-ORO容易进行不易进行R-C-ORO+ROHH+或OH-R-C-ORO+ROH酯交换R-C-OO+RXR-C-ORO+X-亲核取代R-C-RORCOOOHR-C-ORO+RCOOH(容纳电子能力
10、RR)酮的过酸氧化OOO2 NH3OONH2O NH4H+OONH2OH3000CNHOONH33000C形成酰胺与脱水同时进行,得到邻苯二甲酰亚胺。OHNH2Cl-C-OC2H5OOHNH-C-OC2H5OOClCH2Cl(CH3)3CNHNH2ONHNHC(CH3)3CH2ClOOOH2NCOOHHRR=-CH(CH3)2;-CH2+NOOCOOHHRDMFN2,1000CONOOOSNNH2NHZn(OAc)2NNOOONSOCOOC2H5NH2NH2 H2OOCONHNH2C2H5OOCCH2NH2 HClH-C-OCH3O(C2H5)3NH-C-NHCH2COOC2H5ONH2NH2
11、 H2ONNNNCH3CH3SCH2COOC2H5NNNNCH3CH3SCH2CONHNH2NHHOOCCOOCH3NH2+(COCl)2CH2Cl2HNNHOCOOCH3CH3-C-NH2OCH3-C-NHC2H5O+NH3+C2H5NH2H+H2N-C-NH2O+2 RNH2H+RNH-C-NHROCH3NH2NHONHONH2R-C-NHROR-C-OHO+RNH2H+直接酰胺化R-C-XO(RCO)2O+RNH2R-C-NHRO亲核加成-消除R-C-NH2OH+或OH-R-C-NHRO容易进行R-C-ORO+RNH2H+或OH-R-C-NHRO酰胺交换+RNH2R-C-RH+R-C-N
12、HRO(-OH与反式的R对调后再转化为酮式)Beckmann重排NOHNH3R-C=NR-C=NNH3R-C=NHNH2脒 (虚线内为脒基)NC C N=N C CNCH3CH3CH3CH3偶氮异丁腈(AIBN)脂溶性自由基引发剂1.2 NH3HN=C C N=N C C=NHCH3CH3CH3CH3NH2NH22,2-偶氮双(2-脒基丙烷)盐酸盐(AAPH)2HCl2.2 HCl水溶性自由基引发剂(CH3)2N-C N +(C2H5)2NH(C2H5)2NH HCl(CH3)2N-C-N(C2H5)2NH虚线内的结构称为胍,是一种强碱。R-C-GOR-C-OHO+R-C-OHOR-C-GO+
13、OClHOClOOHONOOO-C-CF3OOClHOClOOONOOCH2-C=OHCH3-C-OHOOHCH3-C-CH3OCH2-C=OHCH3BrCH2-C-BrOCH2-C=OBrBr7000C7000CZnCH2=C=OCH2=C=OCH2=C=O+H2O+CH4+ZnBr2活性中间体:烯酮CH2=C=ONuCH2-C=ONuH-Nu-NuCH3-C=ONuCH3-C-NuOR-C-OHOR-C-XOR-C-NH2OR-C-OROR-C-O-C-ROOPX3或SOCl2P2O5/ROH/H+NH3/H+P2O5RCNH2OH2OH2O/OH-H2O/H+或OH-H2O/H+或OH-
14、RCOONaROHROHROHROHROHNH3NH3NH3NH3R-C-NH2NHRNH2R-C-XOR-C-NH2OR-C-OROR-C-O-C-ROORCNH2/PtRCH2OHRCH2OHRCH2OHRCH2NH2RCH2NH2含氧类羧酸衍生物被还原为醇。含氮类羧酸衍生物被还原为胺。C2H5O-C-CH2CH2C-ClOOPd/BaSO4+H2喹啉/SC2H5O-C-CH2CH2C-HOOCH3-C-CH2-C-ClCH3CH3OPd/BaSO4+H2喹啉/SCH3-C-CH2-C-HCH3CH3OR-C-ORONaCH3R-C-CHRO OHHOOCCNH2PtHOOCCH2NH2F
15、eC-C2H5O1.HCN2.(CH3)3SiClFeC-C2H5OSi(CH3)3CN2 LiAlH4(C2H5)2OFeC-C2H5OHCH2NH2NOOH210%Pd/CNHOO R-C-ORONaNa+eR-C-ORO Na双自由基耦合R-C C-RO NaO NaOROR-ORR-C-C-ROO2NaR-C-ONaR-C-ONaH2OR-C-CHROOH类似酮的双分子还原OOHCOOCH3COOCH3Na甲苯CH2-O-C-(CH2)kCH=CH(CH2)7CH3CH-O-C-(CH2)mCH=CH(CH2)7CH3CH2-O-C-(CH2)nCH=CH(CH2)7CH3OOO蒜头果
16、油1.O32.O2O3氧化切断C=CCH2-O-C-(CH2)kCOOHCH-O-C-(CH2)mCOOHCH2-O-C-(CH2)nCOOHOOOCH3OH酯交换得到二酸酯CH3OOC(CH2)lCOOCH3Na二甲苯酯的双分子还原成环l-1HOOZnHCll-1O此方法可以以47%的转化率得到环十五酮R-C-ORONaROHRCH2OHR-C-ORONaNa+eR-C-ORO NaeR-C-ORONaROH-RO-R-C-HONaOR-RO-R-C-HOeR-C-HONaeR-C-HONaRCH2OHROH-RO-R-C-HONaHROH-RO-COOCH3COOCH3NaCH3OHOHO
17、HCOOCH3COOCH3NaCH3OHOHOHSOCl2ClClOCH3OCH3BrONaCH3OH,室温OHCH3OCH3BrCNCH3OSnCl2HClCHOCH3O芳香腈还原为芳香醛 金属还原剂金属还原剂LiAlH4LiBH4NaBH4B2H6LiAlH(t-BuO)3RCOClRCH2OHRCH2OHRCH2OH RCHO(RCO)2ORCH2OHRCH2OHRCH2OHRCH2OH RCOORRCH2OHRCH2OH RCH2OH RCONH2RCH2NH2 RCH2NH2 RCNRCH2NH2 (R=CH3(CH2)11)COOCH3ROORORLiAlH4(R=CH3(CH2)
18、11)CH2OHROOROROFeCOOCH3(CH2)4NH(CH2)2CH3LiAlH4FeCH2OH(CH2)4NH(CH2)2CH3(C2H5OOC)2CHCH2CH2COOCH3LiAlH4OHOHOOHOOOCH3OphCH2OOLiAlH4O-150COHOOCH3OphCH2OClONH2LiAlH4THF,600CClNH2R-C-NH2OR-C-NHO+H+R-C=NHO一般情况下的酸性顺序:RCOOH H2O RCONH2 ROH RC CH NH3NHOOK2CO3NKOO+KHCO3pKa=6.35R-C-NH2O+R-C-ClO(RCO)2OR-COR-CONHHC
19、lRCOOH+CH3-C C-NH2OCH3CH3HNO2H2OCH3-C C-OHOCH3CH3R-C-NH2O+Br2 +NaOHRNH2 +NaBr +Na2CO3R-C-NH2OR-C-NHBrO+Br2+NaOHNaOBr+HBrC=O和Br两个吸电子基团使N上H的酸性更强OH-R-C N BrO同步进行C=N形成Br-脱去R-迁移-Br-O=C=N-R异腈酸酯H2ORNH2+CO2CH3-C C-NH2OCH3CH3Br2NaOHCH3-C NH2CH3CH3C-NH2OCH3Br2NaOHphHNH2CH3phHCH3-CH-CH2-CH3O-C-CH3O5000CCH3=CH-
20、CH2-CH3CH3-CH=CH-CH3+57%43%OOH5000COOHOOH顺式的Hoffmann消除,生成取代少的烯烃,反应过程中无重排。CH3HOAcHD5000CCH3HDCH3HOAcHD5000CCH3H CH3OAc5000CHCH3DC2H5CH2HCH3DC2H5C6H5C6H5DHHAcOAcOC6H5HHC6H5DAcOC6H5HC6H5DH5000CC6H5HHC6H5-AcOD稳定构像C6H5C6H5DHHAcOAcOC6H5HHC6H5DAcOC6H5HC6H5DH5000CC6H5HDC6H5-AcOH稳定构像 DBrHHCH3C2H5RRDBrHC2H5HCH3稳定构像DBrHC2H5HCH3t-BuOKDHCH3C2H5从立体化学角度,卤代烃的Hoffmann消除是反式消除。DBrHHCH3C2H5RRDHOAcC2H5HCH3CH3COONaSN2亲核取代DHOAcHCH3C2H5SR转为顺式DHOAcC2H5HCH3DHCH3C2H5第一步为SN2亲核取代,构型翻转,第二步为酯的热消除,顺式消除,得到的产物与前者相同。OHH+OH2-H2OCH2HCH3H-H+CH3COOHH+OAc 5000C