第三章 酸催化重排

1、酸催化縮合反應(yīng)酸催化縮合反應(yīng)3.1 3.1 酸催化縮合反應(yīng)酸催化縮合反應(yīng) (CH3)3CCl + AlCl3(CH3)3C+ AlCl4(CH3)3C(1) (CH3)2C CH2+ H(2) CH3CHO+HCHH3COHCH2CHOHMe2CCH2FeCl3HF/BF3+CCl3CHOCl+H2SO4CCl3CH()2Cl+H2O2烷基化試劑：烷基化試劑：鹵代烴、烯烴、醇、醛和酮，鹵代烴、烯烴、醇、醛和酮，鹵代苯不能用。鹵代苯不能用。CH3CCH3OOHCH3CH3H2O2+OHHO+CH2SO4CMe3-CH2OH-CH2CN-CH2COOH-CHO-CH2NH2羥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分子內(nèi)F-C烴基化反應(yīng)可用于芳環(huán)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濃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反應(yīng)首先經(jīng)過異丁烯二聚，最后一步是碳正離子從叔丁烷反應(yīng)首先經(jīng)過異丁烯二聚，最后一步是碳正離子從叔丁烷奪取負(fù)氫離子奪取負(fù)氫離子 AlCl3(CH3CO)2O+CS2， 回流BrBrCOCH3+CH3CNZnCl2, HCl(C2H5)2OHClH2O回流.OHHOOHOHHOOHCNHH3COHHOOHCOCH374%87%2. Friedel-Crafts?；磻?yīng)+ OCCCH2CH2Al

4、Cl3CCH2CH2CHOOOOO克萊門森還原CH2CH2CH2CHOO(1)SOCl2(2)AlCl3-四氫萘酮 7989OAlCl3AlCl4CClORCOR+COR(CH3)2C=CH2+(CH3)2C CH2CORAlCl4(CH3)2C CH2CORCl(CH3)2C CHCORMe2NHHCl在在AlCl3存在下烯烴可被酰氯或醋酐酰化，親電部分是一存在下烯烴可被酰氯或醋酐?；H電部分是一個(gè)?；茧x子。個(gè)?；茧x子。CH3COClAlCl3OAlCl4OCl-HClOHClCO+AlCl3-Cu2Cl220oHCOCHOHCHOCC6H6HCOClCH3+CO+HClAlCl3

5、-Cu2Cl220oCH3CHOC3.1.2 3.1.2 醛或酮及其衍生物的反應(yīng)醛或酮及其衍生物的反應(yīng) CH3CHOHH3C CH OHCH3CH OHCH3CHOHCH2CH OHH-HCH2CH OHCH3CHOHH-HCH2CH OHCHCH2H3COHCHOHCHCH2H3COHCHOCHCH2H3COHCHOHCHCH2H3COH2CHO-H2O-HH3CCHOCHCH1. 1. 自身縮合自身縮合 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可繼續(xù)發(fā)生縮合可繼續(xù)發(fā)生縮合3.1.2 3.1.2 醛或酮及其衍生物的反應(yīng)醛或酮及其衍生物的反應(yīng) 2. 2. 交叉縮合交叉縮合 PhC HO+H3CCPhOHCCCPhOHPhHCHOCHCHCH2CHOOHCH CHO-H2OH2CHCHOCH3CHCH2CHOOHCH3CH2CHOCHOKOH1520CH CCHOCH3H2CH2CHCHOCH3枯茗醛枯茗醛 仙客來醛仙客來醛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（曼尼希反應(yīng)曼尼希反應(yīng)）RCCH2OR+CH2ORNRH+RCCHORCH2RNRH 亞甲胺離子亞甲胺離子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) 堿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 顛茄酮 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亞胺極不穩(wěn)定，亞胺極不穩(wěn)定，極容易水解成原極容易水解成原來的醛酮來的醛酮醛酮與伯胺的反應(yīng)醛酮與伯胺的反應(yīng)生成取代亞胺生成取代亞胺HCOH2OCNR+RNH2CNHROH 位位有氫有氫H2OCH2CR(H)ORR(H)NR+ HNR2RRHCH2R(H)NRRROH3.1.4 3.1.4 烯胺烯胺 CCHO+CCNR2Hor OHRHNR2R氨基直接氨基直接與雙鍵碳與雙鍵碳原子相連原子相連CCNR2RCCNR2RO+NHP-CH3-C6H4SO3HC6H6,N+H2ON-(1-環(huán)戊烯基）四氫吡咯四氫吡咯嗎啉哌啶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 - -皮考啉反應(yīng)（皮考啉反應(yīng)（Picoline）NCH3Ph CHONCH2=CHPhZnCl2NCH3ZnCl2NCH2ZnClClHNCH2ZnClH CPhONCH2CHOHH2O HClNCH=CHPhPh機(jī)理：機(jī)理：NCH3PhCHO, ZnCl2100oC, 2hNCHCHPhNCH3ZnCl2, PhC

14、HOH2ONCH=CHPhHCH2OCH2OH+CH2=OHCH2OHC CCH2OHC CH2OH+CH2OHC COH親電加成親電加成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更穩(wěn)定的正離子更穩(wěn)定的正離子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(對(duì)半聯(lián)苯胺對(duì)半聯(lián)苯胺鄰半聯(lián)苯胺鄰半聯(lián)苯胺NHNHH+H3CNHH3CNH2NHNHH3CCH3H+NHH3CCH3H2NNNNNNH2SO3NaNH2SO3NaNHNHH3CCH3H+H2NNH2H3CCH3NaNO2,HClNNH

18、3CCH3NNH2NSO3NaNNNNNH2SO3NaNH2SO3NaH3CCH3OHH3COOCH3H3COOCH3H3COOCH3N2+N2H3COOCH3NH2H2NNHNHH3COOCH3OCH3NO2OCH3OH用苯用苯, 三個(gè)或三個(gè)碳以下的有機(jī)原料和適當(dāng)?shù)臒o機(jī)三個(gè)或三個(gè)碳以下的有機(jī)原料和適當(dāng)?shù)臒o機(jī)試劑合成試劑合成: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歷程：歷程：重排反應(yīng)速率：重排反應(yīng)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 醛發(fā)生醛發(fā)生Schmidt重排反應(yīng)生成腈重排反應(yīng)生成腈 CH3CHOCH3CNHN364%C6H5CHOC6H5CNHN