第三章酸催化重排

1、酸催化缩合反应酸催化缩合反应3.1 3.1 酸催化缩合反应酸催化缩合反应 (CH3)3CCl + AlCl3(CH3)3C+ AlCl4(CH3)3C(1) (CH3)2C CH2+ H(2) CH3CHO+HCHH3COHCH2CHOHMe2CCH2FeCl3HF/BF3+CCl3CHOCl+H2SO4CCl3CH()2Cl+H2O2烷基化试剂：烷基化试剂：卤代烃、烯烃、醇、醛和酮，卤代烃、烯烃、醇、醛和酮，卤代苯不能用。卤代苯不能用。CH3CCH3OOHCH3CH3H2O2+OHHO+CH2SO4CMe3-CH2OH-CH2CN-CH2COOH-CHO-CH2NH2羟甲基氰甲基羧甲基氨甲基

2、醛基 HCHOHCl+H3PO4CH3COOHCH2ClH2O+77%H2SO4+H2O88%CH3CH2OOCH3H3COHCH3CH3H3CSiO2, H3PO4CH2Cl2, 25 oC, 2h82%CH3H3C分子内F-C烃基化反应可用于芳环稠合(CH3)3CCl(CH3)3CCH2CH2ClAlCl3-10 oC+CH2=CH2(CH3)3CClAlCl3(CH3)3CAlCl4+(CH3)3C+(CH3)3CCH2CH2CH2=CH2(CH3)3CCH2CH2Cl+AlCl4(CH3)3CCH2CH2+AlCl3H3CC=CH2H3C+CHCH3CH3CH3浓H2SO4或HF010

3、 oC(CH3)3CHCH2C(CH3)3(CH3)3C(CH3)3CCH2C (CH3)2H(CH3)2C=CH2(CH3)2C=CH2HC(CH3)3(CH3)3CCH2CH(CH3)2+(CH3)3C反应首先经过异丁烯二聚，最后一步是碳正离子从叔丁烷反应首先经过异丁烯二聚，最后一步是碳正离子从叔丁烷夺取负氢离子夺取负氢离子 AlCl3(CH3CO)2O+CS2， 回流BrBrCOCH3+CH3CNZnCl2, HCl(C2H5)2OHClH2O回流.OHHOOHOHHOOHCNHH3COHHOOHCOCH374%87%2. Friedel-Crafts酰基化反应+ OCCCH2CH2Al

4、Cl3CCH2CH2CHOOOOO克莱门森还原CH2CH2CH2CHOO(1)SOCl2(2)AlCl3-四氢萘酮 7989OAlCl3AlCl4CClORCOR+COR(CH3)2C=CH2+(CH3)2C CH2CORAlCl4(CH3)2C CH2CORCl(CH3)2C CHCORMe2NHHCl在在AlCl3存在下烯烃可被酰氯或醋酐酰化，亲电部分是一存在下烯烃可被酰氯或醋酐酰化，亲电部分是一个酰基正碳离子。个酰基正碳离子。CH3COClAlCl3OAlCl4OCl-HClOHClCO+AlCl3-Cu2Cl220oHCOCHOHCHOCC6H6HCOClCH3+CO+HClAlCl3

5、-Cu2Cl220oCH3CHOC3.1.2 3.1.2 醛或酮及其衍生物的反应醛或酮及其衍生物的反应 CH3CHOHH3C CH OHCH3CH OHCH3CHOHCH2CH OHH-HCH2CH OHCH3CHOHH-HCH2CH OHCHCH2H3COHCHOHCHCH2H3COHCHOCHCH2H3COHCHOHCHCH2H3COH2CHO-H2O-HH3CCHOCHCH1. 1. 自身缩合自身缩合 CH3CCH3O2H3CCH3CCHCCH3OH+HO HCH3CCH=C(CH3)2HCH2=CCH=C(CH3)2OH(CH3)2C=CHCOCH3+H3OCH2=CCH=C(CH3)

6、2OHCH3CCH3OH(CH3)2C=CHCCH2C(CH3)2OHO HC=CHCOCH=CCH3CH3H3CH3C可继续发生缩合可继续发生缩合3.1.2 3.1.2 醛或酮及其衍生物的反应醛或酮及其衍生物的反应 2. 2. 交叉缩合交叉缩合 PhC HO+H3CCPhOHCCCPhOHPhHCHOCHCHCH2CHOOHCH CHO-H2OH2CHCHOCH3CHCH2CHOOHCH3CH2CHOCHOKOH1520CH CCHOCH3H2CH2CHCHOCH3枯茗醛枯茗醛 仙客来醛仙客来醛PhC HO+H3CCCH2CH3ONaOHCCCCH2CH3OHPhHCCCCH3OHPhCH3

7、H+CH3NO2HOAc + NH4OAc100, 3h, 或70,overnightXCHOXCH=CHNO2ArCHOH2CCNX+NH4OAc36minCNArCH=CXX: CF3, MeO, F, Cl X: CN, CONH2 3.1.3 3.1.3 Mannich reaction（曼尼希反应曼尼希反应）RCCH2OR+CH2ORNRH+RCCHORCH2RNRH 亚甲胺离子亚甲胺离子OH+CH2OMe2NH+HOHCH2NMe2CH2NMe2Me2NCH2NH+CH2OMe2NH+HNHCH2NMe2CH3CH(CO2H)2CH2O(CH3)2NH+HH2O(CH3)2C(CO

8、OH)2CH2N(CH3)2NCH2OMe2NH+CH3HN NC CH H2 2C CH H2 2N NMMe e2 2C2H5O2CCO2C2H5OC2H5C2H5+2 CH2ONH2H3CHCH2OHC2H5O2CCO2C2H5OC2H5C2H5H2CNHCH3C2H5O2CCO2C2H5OC2H5C2H5NCH3PhCC-H=CH2OMe2NH+HH2OPhC=CCH2NMe2OCH2N +OHN+CH2OHC6H5COCH3CH2OR2NHH+C6H5COCH2CH2NR2+C6H5COCHCH2H2/NiC6H5COCH2CH3-R2NH(CH3)2CHCHCHOCH2N(CH3)

9、2CH3CH2CCHOCH2H3CCOCH3+CH2O+H+H3CCCH2H2CON(CH3)2H(1) 碱HN(CH3)2H3CCCHCH2O RCOCH3+CH2O+H+RCCH2H2CON(CH3)2HHN(CH3)2RCCH CH2O NHCH2O+Me2NHCH3COOHH2ONHCH2N(CH3)2（CH3)2SO4NHCH2N(CH3)3CNOHNHCH2COOHH2NCOOCHCHCH2N(CH3)2CH3CH3CH3COCH2CH3CH2O-H2O(CH3)2NHCH3COCHCH2N(CH3)2CH3CH3CHCCH2N(CH3)2CH3LiAlH4OHH2NCOOHCHO

10、CHOONH2H3CCOOHCOOH+ONH3CCOOHCOOHH+ONH3C 颠茄酮 C6H5COCH2CH3COCHCH2N(CH3)2C6H5CH2CCH2CH3OCH3COCHCH2N(CH3)2C6H5CH2CCH2CH3OCH3+COHCHCH2N(CH3)2C6H5CH2CH3HO CCH2CH3OCOCH2CH3HN(CH3)2HCHO+COCHCH2N(CH3)2CH3C6H5CH2MgBr+SN(CH3)2OHSSN(CH3)2O(CH3CO)2OSCOHCHO, HN(CH3)2H+SN(CH3)2OHNaBH4F3CNOHCO+H2OCNH+NH3HCO+H2OCNR+

11、RNH2亚胺极不稳定，亚胺极不稳定，极容易水解成原极容易水解成原来的醛酮来的醛酮醛酮与伯胺的反应醛酮与伯胺的反应生成取代亚胺生成取代亚胺HCOH2OCNR+RNH2CNHROH 位位有氢有氢H2OCH2CR(H)ORR(H)NR+ HNR2RRHCH2R(H)NRRROH3.1.4 3.1.4 烯胺烯胺 CCHO+CCNR2Hor OHRHNR2R氨基直接氨基直接与双键碳与双键碳原子相连原子相连CCNR2RCCNR2RO+NHP-CH3-C6H4SO3HC6H6,N+H2ON-(1-环戊烯基）四氢吡咯四氢吡咯吗啉哌啶NHONHNHOHO HR2NHHON HR2HONR2HNR2H2OH2OH

12、N R2HHNR2HOH3C+p-CH3C6H4SO3HC6H6,NH3C+NH3C8515NH3.1.43.1.4 烯胺烯胺 OH3C+p-CH3C6H4SO3HC6H6,NH3CNHOH3CH2O / H+RX1.2. H2O / H+CCORRCOCl1.2.CCCORORO1.2.ROCOH2O / H+H2O / H+RRR CCNR2RONHH+N(1)Br(2) H3O+ONCH3I, CH3OH,NH3CI水解OCH3ONHH+NONCH3(CH2)5CClON(C2H5)3NOHCO(CH2)5CH3NOCO(CH2)5CH3水解OCO(CH2)5CH375%NH3CCH3C

13、H2OHNH3CCH2CHCNHNCH2CH2CNH3COH3CCH2CH2CN:+回流水解65%CH2=CHCNN+ CH2=CHCO2CH3CH3CNH2OC2H5CHCHOCH2CH2CO2CH3C2H5CH=CHNC2H5CHCHCH2CHCO2CH33.1.53.1.5 - -皮考啉反应（皮考啉反应（Picoline）NCH3Ph CHONCH2=CHPhZnCl2NCH3ZnCl2NCH2ZnClClHNCH2ZnClH CPhONCH2CHOHH2O HClNCH=CHPhPh机理：机理：NCH3PhCHO, ZnCl2100oC, 2hNCHCHPhNCH3ZnCl2, PhC

14、HOH2ONCH=CHPhHCH2OCH2OH+CH2=OHCH2OHC CCH2OHC CH2OH+CH2OHC COH亲电加成亲电加成HCHOH2OOCCH2COCH2HOBrPhCH(OH)CH2BrTsOH, KHSO4-H2OHCHOOOPhBrOOPhNH2H+PhCHOHCHNH2CH2OH拆分CHCl2COClPh CHOHCHNHCOCHCl2CH2OHD-(-)-氯霉素PhCH=CH2PhCH=CHBrPh=NO2NH3CH2O+HCH3CHCHCH2OHOHCH3CH=CHCH3CH3PhCH-CH2CH2OHOHHCHOHCHO+HNa-ROHPh(CH2)3OHPhC

15、H=CH22CH2OOOPh3.2 3.2 酸催化分子重排酸催化分子重排 CH3CCCH3H3CCH3OHOHCH3CCH3CCH3CH3OH+H2OCH3CCCH3H3CCH3OHOHH+CH3CCCH3H3CCH3OHOH2CH3CCCH3H3CCH3OHH2O CH3CCCH3H3CCH3OH H+CH3CCH3CCH3CH3O CH3H2O CH3更稳定的正离子更稳定的正离子CPhPhCCH3CH3OHCPhPhCCH3OCH3CPhPhOHCCH3CH3OHH2SO4CPhCH3OHCHHOHH+H+CPhOCH2CH3CPhCH3CHHOHCHPhCH3CHOHCHPhCH3CHO

16、H2SO4OHHOOOMgOHH3OOOMg2+OHOHH3OH2OZn-Hg/ HClOOHOH2OH苯CH3CCH3OHCCH3CH3NH2HNO2CH3CCH3OHCCH3CH3NN-N2CH3CCH3CCH3CH3OHCH3CCH3CCH3OCH3CH3CCH3CCH3OHCH3-H+OOHCH2NO2CH2NH2HOOCH2HO+CH3NO2OHH/NiNaNO2/HCl(CH3)3CCH2OHH+(CH3)3CCH2OH2-H2O(CH3)3CCH2(CH3)2CCH2CH3-H+(H3C)2CCHCH3CCCCCCCCCCCCONOHHHNONH2OHCRNR1OHH+CRNR1

17、OH2-H2OCRNR1CNR1RH2OCNR1RH2O-H+CNR1ROHCNR1HORHHNOHHHNHOH110oCHHNHOHHHNHO110oCOCNH2OH HCl+HCOOH/SiO2OCNHCPCl5NCOHNO2NO2CHNONO2NOHNHNHH+H2NNH2NHNHH+H2NNH2NHNHCH3H3CH2NNH2H3CCH3H2NNH2H3C(对半联苯胺对半联苯胺邻半联苯胺邻半联苯胺NHNHH+H3CNHH3CNH2NHNHH3CCH3H+NHH3CCH3H2NNNNNNH2SO3NaNH2SO3NaNHNHH3CCH3H+H2NNH2H3CCH3NaNO2,HClNNH

18、3CCH3NNH2NSO3NaNNNNNH2SO3NaNH2SO3NaH3CCH3OHH3COOCH3H3COOCH3H3COOCH3N2+N2H3COOCH3NH2H2NNHNHH3COOCH3OCH3NO2OCH3OH用苯用苯, 三个或三个碳以下的有机原料和适当的无机三个或三个碳以下的有机原料和适当的无机试剂合成试剂合成:BrBrOCH3H3CONH2H2NBrBrBrNHNHBrBr2FeCl3H2SO4BrHO3SH2SO4HNO3BrNO2HO3SBrNO2ZnNaOHH+NaNO2HClH+H2OOHHOBrBrOCH3H3COBrBrCH3IK2CO3BrH3O+Schimdt

19、COROHH2SO4COHROHCOROH2COR+ H2OCORHN3+-H+CORNNN-N2CORNNCORH2ORNH2 + CO2a羧酸：羧酸：RNH2+RCNONNRCOHOH2ON2HN3H2SO4CO2+ 烷基重排到烷基重排到N原子上原子上HN3H2SO4CH3(CH2)4COOHCH3(CH2)4NH2COOHNH2CH2COOHCOOHCH2HN3H2SO4NH2HN3H2SO4H3COHH3CCOOHH3COHH3Cb酮的重排：酮的重排：H2SO4HN3CORRRCONHR + N2CORR1H2SO4HN3RCONHR1R1CONHR+ N2HN3CORR+COHRRNNN-N2COHRRNNCRROHRCONHR历程：历程：重排反应速率：重排反应速率： 二烷基酮二烷基酮烷基芳基酮烷基芳基酮二芳基酮二芳基酮芳基烷基酮重排一般是芳基重排到氮原子上。芳基烷基酮重排一般是芳基重排到氮原子上。H2SO4HN3OCH3NHCCH3OOOOHN3HNHOc 醛发生醛发生Schmidt重排反应生成腈重排反应生成腈 CH3CHOCH3CNHN364%C6H5CHOC6H5CNHN