1、第三章 酸催化縮合和分子重排3.1 酸催化縮合反應(yīng)3.1.1 Friedel-Crafts反應(yīng)一、烷基化反應(yīng) 包括芳烴、烯烴、醛、酮和醇等在催化劑無(wú)機(jī)酸或lewis酸催化下，生成正離子并與親核試劑作用，從而生成碳碳或碳氮等鍵的反應(yīng)。1、芳烴的烷基化CH2Cl+HClAlCl3+AlCl3H2CCHCH3H+AlCl3H+CH2CH3CH3CH2OH+ H2OCCl3CHO +Cl2H2SO4Cl3CHCCl2+ H2OH2SO4CH3CCH3OOH2+CCH3CH3HOOH+ H2OH2SO4OOCH388%OHH3PO4H2C50%二、?；磻?yīng)1) 合成酮CClO+OAlCl3+AlCl3

2、OOOHOOCO1)Zn-Hg/HCl2) H2SO4,OH2SO4,OOOCH3CH3COOHP2O5OCH3COCH3CH3COOHP2O5OCH3COCH3COCH3NO2CH3COClAlCl3OCH3OCH3COCH3CH3COClAlCl3NO2NO2Br+ (CH3CO)2OAlCl3CS2,BrH3COCOHOHHOZnCl2,HCl(C2H5)2O+CH3CNOHOHHOCNH.HClH3CH2OOHOHHOCOH3CN(CH3)2+CONHC6H5POCl3(H3C)2NCC6H5NC6H5H2OHCl(H3C)2NCC6H5O活潑底物可以用腈或酰胺做酰化試劑烯烴的?；?/p>

3、CORCl+ AlCl3COR+AlCl4-COR+RO-H+ROAlCl4-ROCl-HClMe2NH2）合成醛AlCl3CH3+ HCl + COCH3CHOAlCl3-CuCl200HCOOH + ClSO3H+ HCl + COH2SO4 HCl + COHCOClCHOCH3CH3H3CBF3+ FCHOCH3CH3H3CCHOOCH31)HCN,HCl,AlCl32)H2OOCH3CHO氫氰酸劇毒，可用氰化鋅代替HCl + HCNAlCl3HNCHClRRHCHNH2ORCHO+ NH3反應(yīng)歷程：1)Zn(CN)2,HCl,AlCl32)H2OOHH3CCH(CH3)2OHH3CC

4、H(CH3)2CHOCH3CH3H3CCH3CH3H3C+Cl2CHOCH3TiCl4CH2Cl2CH3CH3H3CClCHOCH3CH3CH3H3CCHOCH3ClH2OCHO3.1.2 醛、酮及其衍生物的反應(yīng)無(wú)機(jī)酸的作用：1、提高羰基對(duì)親核試劑的加成活性； 2、促使羰基化合物的烯醇化。一、自身縮合2CH3CHOH+CH3CHCH2CHOOH-H2OCH3CHCHCHOCH3CHOCH3CHCH2CHOOHCH3CHCHCHOH+CH3CHOHCH3CHOHCH3CHOH+H2CHCHOH-H+CH2CHOHHCCH2OH+CH3CHOHCHCH2CHOHHOCH3-H+CH3CHCH2CH

5、OOHH+CH3CHCH2CHOOH2-H3O+反應(yīng)歷程：COH3CCH32H+CH3CCH3CHCCH3OCOH3CCH3CH3CCH3CHCCHOCCH3CH3二、交叉縮合CHOOH+OH3CHClCHOCHCXArCHO+ CH3NO2HOAc+NHOAcXArCHCHNO2三、酮與酰鹵或酸酐的縮合-H+CH3COCH3BF3CH3CCH2OBF3HCH3COCH2BF3OH3CCH3CCOOBF3OH3CCH3CCOOBF3CH3CO+CH3COOBF3-CH3COCH2BF3CH3CO+CH3COCH2COCH3+ BF3CH3COCH2R +(CH3CO)2OBF3CH3COCHC

6、OCH3R不對(duì)稱(chēng)酮發(fā)生在次甲基上3.1.3 Mannich反應(yīng)一、Mannich反應(yīng) 具有烯醇式或潛在烯醇式結(jié)構(gòu)的化合物，與醛（通常為甲醛），在酸催化下，與第一第二胺反應(yīng)，生成胺甲基化衍生物的反應(yīng)，叫做Mannich反應(yīng)。RCOCH3+ HCHO+Et2NH2ClRCOCH2CH2NEt2 Cl+ H2ONaOHRCOCH2CH2NEt2反應(yīng)歷程：HCHO + H+H2COHH2COHMe2NHH2COH+Me2N+HCH2OH-H2OMe2N+=CH2Me2NCH21、酸活化甲醛，催化甲醛和胺的加成2、使含有活潑氫的化合物烯醇化PhCOCH3H+PhCOHCH2H-H+PhCCH2OH3、加

7、成PhCCH2OH+Me2N+=CH2-H+PhCOCH2CH2NMe2PhCOCH=CH2 + Me2NHOH+ HCHO + Me2NHH+OHMe2NH2CCH2NMe2CH2NMe2除了具有活潑氫的醛酮可以反應(yīng)之外，其他化合物如-二元酸、 -氰基酸、 -酮酸、甚至-甲基吡啶、-萘酚、呋喃、吡咯和他們的衍生物也能反應(yīng)。CH3CH(COOH)2+ HCHO + Me2NHH+CH3C(COOH)2CH2NMe2NCH3+ HCHO + Me2NHH+NCH2CH2NMe2PhCCH+ HCHO + Me2NHH+PhCCCH2NMe2苯乙炔也可以反應(yīng)RCOCH3 + ArCHO + ArN

8、H210%NaHCO33）020RCOCH2CH(Ar)NHAr二、在合成中的應(yīng)用1）制備，-不飽和羰基化合物RCOCH3+ HCHO+Et2NH2ClRCOCH2CH2NEt2 Cl+ H2ORCOCH=CH22)Mannich堿或季銨鹽的轉(zhuǎn)換NH+ HCHO + Me2NHH+NHCH2NMe2(CH3)2SO4NHCH2NMe31)CN-2)OH-NHCH2COOHNHCH2NMe3CH3CONHCH(COOEt)2EtO-H+CH3CONHC-(COOEt)2CH3CONHC-(COOEt)2+NHCH2C(COOEt)2NHCOCH31)OH-,2)H+3)NHCH2CHCOOHNH

9、23）合成生物堿H2CH2CCHOCHO+CH3NH2+COH2CH2CCOO-COO-NH3C-OOCCOO-OH3O+NH3CO托品酮托品酮具有鎮(zhèn)痛、解毒和解除痙攣等作用。托品酮具有鎮(zhèn)痛、解毒和解除痙攣等作用。NH3COZn-HINH3CHOHPhCH(CHO)COOHNH3CHOCOCHPhCHOKBH4CHCl3NH3CHOCOCHPhCH2OH常用于麻醉前給藥，眼科中用作擴(kuò)大瞳孔用藥，搶常用于麻醉前給藥，眼科中用作擴(kuò)大瞳孔用藥，搶救有機(jī)磷中毒用藥救有機(jī)磷中毒用藥H2CH2CCHOCHO+CH3NH2+COH2CH2CCOOCH3COO-NH3CCOOCH3O1)H+2)-CO21)H

10、2)PhCOClNCOOCH3OCOPh古柯堿80%H3C+CH3NH2+COH2CH2CCOO-COO-H2CCH2CH2CHOCHONH3CO1)-2H2O2)-2CO21)H2)PhCOClNH3CONH3COCOPh3.1.4 烯胺一、烯胺的生成NHNHONHONH+p-CH3-C6H4SO3HC6H6,N+ H2OOH3CNH+p-CH3-C6H4SO3HC6H6,NH3CNH3C+85%15%二）烯胺在有機(jī)合成中的應(yīng)用NCH3I,CH3OHNCH3I-OCH3NH3C+H2CCHCNEtOHNH3CCH2CHCNHNH3CCH2CH2CNOH3CCH2CH2CN注意：反應(yīng)發(fā)生在取代

11、基較少的注意：反應(yīng)發(fā)生在取代基較少的-碳上碳上C2H5CHCHN+H2CCHCOOCH31) CH3CN2) H3O+C2H5CHCHOCH2CH2COOCH3NOCH3(CH2)5COClN(C2H5)3NONOHCO(CH2)5CH3CO(CH2)5CH3OCO(CH2)5CH33.1.5 -皮考啉反應(yīng)NCH3ZnCl2,PhCHONCHCHPhNCH3ZnCl2,PhCHONCH=CHPh3.1.6 Prins 反應(yīng)HCHO + H+H2COHCH2OH+CH2OHCCH2OHH2O-H+CCCH2OHOHHCHO-H2OOCH2OCCH2CPhHCCH22HCHO+H+OOPh該反應(yīng)提

12、供較原來(lái)烯烴多一個(gè)碳原子醇的合成方法該反應(yīng)提供較原來(lái)烯烴多一個(gè)碳原子醇的合成方法氯霉素的合成氯霉素的合成PhHCCH2HOBrCHCH2BrPhOHTsOH,KHSO4-H2OPhHCCHBrHCHOOOPhBrNH3OOPhNH2H+CHOHPhCNH2HCH2OH CHCl2COClCHOHPhCNHCOCHCl2HCH2OHD-(-)-3.2 酸催化分子重排酸催化分子重排3.2.1 頻哪醇頻哪醇-頻哪酮重排頻哪酮重排CH3CCH3OHCCH3CH3OH(1) H+(2) -H2OCH3CCH3CCH3CH3OHCH3CCH3CCH3OHCH3-H+CH3CCH3CCH3OCH3CPhCH

13、3OHCHHOHH+H+CPhOCH2CH3CPhCH3CHHOHCHPhCH3CHOHCHPhCH3CHO1）生成穩(wěn)定碳正離子；）生成穩(wěn)定碳正離子；2）親核性更強(qiáng)的原子或基團(tuán)發(fā)生遷移，一般）親核性更強(qiáng)的原子或基團(tuán)發(fā)生遷移，一般ArRH。CPhPhCCH3CH3OHCPhPhCCH3OCH3CPhPhOHCCH3CH3OHH2SO4ZnCl2CPhPhOHCCH3CH3CPhOCCH3CH3PhLewis酸更容易和甲基連接的碳羥基結(jié)合。酸更容易和甲基連接的碳羥基結(jié)合。OMg(Hg)OHH3OOOMg2+OHOHH3OH2OZn-Hg/ HClOOHOH2OHO由合成3.2.2 吶吶咵咵重排和反

14、吶重排和反吶咵咵重排重排CH3CCH3OHCCH3CH3NH2HNO2CH3CCH3OHCCH3CH3NN-N2CH3CCH3CCH3CH3OHCH3CCH3CCH3OCH3CH3CCH3CCH3OHCH3-H+吶吶咵咵重排重排:反吶反吶咵咵重排重排:(CH3)3CCH2OHH+(CH3)3CCH2OH2-H2O(CH3)3CCH2(CH3)2CCH2CH3-H+(H3C)2CCHCH3CCCCCCCCCCCC3.2.3 Beckmann重排重排CRNR1OHH+CRNR1OH2-H2OCRNR1CNR1RH2OCNR1RH2O-H+CNR1ROHCNR1HOR和羥基在異側(cè)的烴基重排和羥基在異

15、側(cè)的烴基重排HHNOHHHNHOH+110 C C110 C CH+HNNHHHHHOO利用貝克曼重排，可以合成己內(nèi)酰胺、取代酰胺和利用貝克曼重排，可以合成己內(nèi)酰胺、取代酰胺和-氨基酸等重要的合成中間體。氨基酸等重要的合成中間體。ONH2OHrt.NOHBpy BF4/PCl3353K,2hNHOMeMeCO2CH3CHMe268CH3COClAlCl3,C6H5NO2MeMeCO2CH3CHMe2COCH3NH2OH HClMeMeCO2CH3CHMe2CCH3NOH1)HCl-HOAc-Ac2O,25 C C2) H3O+,62%MeMeCO2CH3CHMe2NH2CNOHNO2HClH+

16、CNOH2+NO2-H2OCNNO2NCNO2H2ONCNO2OH2NCNO2OHHNCNO2OHNCNO2O3.2.4 烯丙基重排烯丙基重排H2CCHCH2OHH2CCHCH2ClH2CCHCH2CH2CHCH21 2 31 2 3H+-H2O-Cl烯丙基正離子的產(chǎn)生烯丙基正離子的產(chǎn)生:-ClCH3CHCHCH2ClCH3CHCHCH2CH3CHCHCH2H2OH2OCH3CHCHCH2OH2-H+CH3CHCHCH2OHCH3CHCHOH2CH2-H+CH3CHCHOHCH2SN1歷程：歷程：H2CCHCHCH3Cl(C2H5)2NH +CH2CHCHCH3(C2H5)2NCH2CHCHC

17、H3(C2H5)2N(C2H5)2NHClCH2CHCHCH3+SN2SN2SN2和和SN2為競(jìng)爭(zhēng)反應(yīng)，當(dāng)空間位阻較大時(shí)發(fā)生為競(jìng)爭(zhēng)反應(yīng)，當(dāng)空間位阻較大時(shí)發(fā)生SN23.2.5 聯(lián)苯胺重排聯(lián)苯胺重排 氫化偶氮苯重排為氫化偶氮苯重排為4，4-二氨基聯(lián)苯的反應(yīng)稱(chēng)為聯(lián)二氨基聯(lián)苯的反應(yīng)稱(chēng)為聯(lián)苯胺重排。苯胺重排。NHNHH+H2NNH2NHNH2H+NNHHHHNNHHHHNNHHHHNNHHHHHHNHHNHHHHNHHHNHHH-2H+H2NNH2NHNHH+H2NNH2NHNHCH3H3CH2NNH2H3CCH3H2NNH2H3C(不發(fā)生交叉式重排，該重排為分子內(nèi)重排。不發(fā)生交叉式重排，該重排為分子內(nèi)

18、重排。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+NHH3CCH3H2NNNNNNH2SO3NaNH2SO3NaNNNNNH2SO3NaNH2SO3NaH3CCH3NNNNOHOHNH2NaO3SNH2SO3NaNaO3SSO3NaNHNHH3CCH3H+H2NNH2H3CCH3NaNO2,HClNNH3CCH3NNH2NSO3NaNNNNNH2SO3NaNH2SO3NaH3CCH3如：如：3.2.6 Schimdt 重排重排 在強(qiáng)酸存在下，羧酸、醛酮等與疊氮酸作用，在強(qiáng)酸存在下，羧酸、醛酮等與疊氮酸作用，生成伯胺、酰胺或腈的反應(yīng)稱(chēng)為施密特

19、重排。生成伯胺、酰胺或腈的反應(yīng)稱(chēng)為施密特重排。RCOOH + HN3H2SO4C6H6RNH2 + CO2 + N2COROHH2SO4COHROHCOROH2COR+ H2OCORHN3+-H+CORNNN-N2CORNNCORH2ORNH2 + CO2羧酸：羧酸：H2SO4COOHCOOHHN3NH2NH2COOHH2SO4HN3NH2OHH3CH3CCOOHH2SO4HN3OHH3CH3CNH2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：