1、第三章第三章 酰化反应酰化反应(Acylation Reaction)在有机化合物分子中的碳、氧、硫等原子上引入酰基在有机化合物分子中的碳、氧、硫等原子上引入酰基的反应。酰基的引入可分为直接酰化和间接酰化。的反应。酰基的引入可分为直接酰化和间接酰化。(1)直接亲电酰化：RCZOSHRCSOZHZ=Hal.,OCOR1,OH,OR1,NHR1 ect.S=R2NH,R2O,Ar ect.(2)直接亲核酰化：s-BuLiCO-110oCs-BuCOLiO-110oCNH4ClOHCOBu-s(88%)(3)直接自由基化：H3CCHOBz2O29095oC,8hH3CCO.R1HCCH2CH3COC
2、H2CH2R1(1)间接亲电酰化：N(CH3)2RRNHCCl.OPOCl2-HOPOCl2N(CH3)2CHClNRRH2ON(CH3)2CHORRNHHCl(2)间接亲核酰化：R CHOHSHSSSRn-BuLiSSRLiR1XSSRR1H2O/HgCl2R1CRO亲核能力：RCH2 RNH RO RNH2ROH酰化能力：RCOClO4 RCOBF4 RCO.Hal(RCO)2O RCOOR1,RCOOH RCONHR1第一节第一节 氧原子上的酰化反应氧原子上的酰化反应一、醇的一、醇的O-O-酰化酰化AA11C OHC OH2CC OHRCOOHH2OHCOR 醇的醇的O酰化可得酯，一般情
3、况下，伯醇易于反应，酰化可得酯，一般情况下，伯醇易于反应，仲醇次之，而叔醇则由于立体位阻较大且在酸性介质中仲醇次之，而叔醇则由于立体位阻较大且在酸性介质中易于脱去羟基而形成叔碳正离子，使酯化按易于脱去羟基而形成叔碳正离子，使酯化按AA11（表示（表示酸催化下烷氧断裂的单分子反应）历程而难于完成。酸催化下烷氧断裂的单分子反应）历程而难于完成。醇的酰化常用酰化试剂：羧酸、羧酸酯、酸酐、醇的酰化常用酰化试剂：羧酸、羧酸酯、酸酐、酰氯、酰胺、烯酮等。酰氯、酰胺、烯酮等。1.羧酸为酰化剂羧酸为酰化剂 一般为一般为AAC2（表示酸催化下酰氧断裂的双分子反应）（表示酸催化下酰氧断裂的双分子反应）机理：机理：
4、AAC2 机理：R COOHR COHOHR COROHOHR COROHOH2R1OHHH-H2OR COHOR1R COOR1-H（1）质子酸催化法HOOCH2CH2CCHCOOHNH2ROH/HBF4/Na2SO42560oCROOCH2CH2CCHCOOHNH2(34%94%)CH2COOHOHTsOH/PhH,10minOO(97%)(2)Lewis 酸催化法：CHCHCOOHCH3OHBF3/Et2O,21hCHCHCOOCH3(94%)EtCOOHn-BuOHAlCl3/polystyreneEtCOOBu-n(97%)ROHCH3COOHSc(OTf)3r.t.CH3COOR(
5、88%99%)(3)Vesley法：CH3COOHCH3OHVesley法10minCH3COOCH3(94%)CH3COOHn-C4H9OHVesley法 17hCH3COOC4H9-n(100%)(4)DCC及其类似物脱水法：RCOOHNC NNHC NRCOORCOONHNHRCOO CHNHN.RCOORCOOH(RCO)2OHNCOHNR1OHR COO R1HHN COHNRCOOR1HPhCOOHPhOHDCCPhCOOPh(10%)PhCOOHPhOHPhCOOPhDCC/PPY(94%)OOCH2OHCOOHIDCC/DMAP25oCOOH2C O COI(96%)若在反应系
6、统中加入对二甲氨基吡啶（若在反应系统中加入对二甲氨基吡啶（DMAP）、）、4吡咯烷基吡啶（吡咯烷基吡啶（PPY）等催化剂则使活性增加，）等催化剂则使活性增加，收率提高，反应可在室温进行。收率提高，反应可在室温进行。(5)DEAD 法（偶氮二羧酸二乙酯法）法（偶氮二羧酸二乙酯法）利用偶氮二羧酸二乙酯和三苯膦反应用以活化醇来制备羧酸酯。利用偶氮二羧酸二乙酯和三苯膦反应用以活化醇来制备羧酸酯。DEAD:NNCOOC2H5COOC2H5NNHOOOOHHOHOCOOHNO2DEAD/Ph3Pr.t.,1hNNHOOOOHHOOCOO2N(83%)OOHOOOOHDEAD/PhCOOHK2CO3/MeO
7、H(70%)2.羧酸酯为酰化剂RCOOR1R2OHRCOOR2R1OHRCOOR1RCOOR1R2COOHR2COOR3R2COOR1RCOOR3RCOOHR2COOR1(醇解)(酸解)(酯交换)醇的酯交换机理:RCOOR1HRCOOHR1R2OHR2OHCOROHR1R1OHRCOOHR2HRCOOR2RCOOR1R2ORCOOR2OR1RCOOR2R1Oi-PrOHOOCOOMeMeOOCTi(OPr-i)470oC,3hOOCOOPr-ii-PrOOC(91%)MeOC12H25OOOHArDMAPOArC12H25OOAr-=1-萘基(97%)COOMeOHPhP(NCH3CH2CH2
8、)3Nr.t.,24hOOPh(91%)HOOHEtCOOMeNaHSO4-SiO22.2h,70oCOOHEtO(92%)为适合合成复杂的化合物如肽、大环内酯类等天然化为适合合成复杂的化合物如肽、大环内酯类等天然化合物，开发了许多酰化能力较强的活性羧酸酯为酰化剂。合物，开发了许多酰化能力较强的活性羧酸酯为酰化剂。（1）羧酸硫醇酯）羧酸硫醇酯RCOOHNS SNPh3PRCOOHNS COClRCOClNSHEt3NNS COREt3NNS(CH2)nOHONS(CH2)nOOHXylNSC(CH2)nOOHO(CH2)nOn=14(88%)NHSOOHOCOOHOHCH3OOOOOOHCH3
9、OO(75%)NS CORPh3P/HOAc/THF（2）羧酸吡啶酯）羧酸吡啶酯NCH3ClINCH3OCOClINCH3OOCRIEt3N/RCOOH,7.5-8hEt3N/RCOOH/DMAPNCH3ClIHO(CH2)nCOOH,7.5-8hEt3NNCH3OIC(CH2)nOHOn(H2C)OONOCH3n=5(89%);n=11(69%)OHOHOHC6H13-nOOHC6H13-n(95%)NCH3ClNHOPhEt3N/TsOH3.酸酐为酰化剂酸酐为酰化剂 酸酐为强酰化剂，反应具有不可逆性，酰化时常在酸酸酐为强酰化剂，反应具有不可逆性，酰化时常在酸或碱催化下进行。或碱催化下进行。
10、(CH3CO)2OH(CH3CO)2OHCH3COCH3COOHCH3COR1OHCH3COOR1H(CH3CO)2ON-CH3COONCOCH3R1OHCH3COOR1NHOOHAc2OPy,18hOOAc(81%)Ac2OPPYNNCOCH3NNCOCH3NNC OH3COHOOHPhCCH3OHPhOCH3OCH3OH(PhCO)2O Ac2O (CH3CH2CO)2O Ac2O Ac2OP(MeNCH2CH2)3N DMAP DMAP/Et3N PPY/Et3N PPY/Et3N99 95 94 92 86酰化剂催化剂收率/%OH（PhCO）2O/Bu3P/CH3CN23oC 1hOC
11、OPh（88%）C9H19OHC9H19OAcAc2O/Sc(OTf)3-20oC,5.5h(94%)Ac2O/DMAPr.t.,5.5h(1%)CH2OHHOAc2OBF3.Et2OPyCH2OAcHOCH2OAcAcO(68%)(62%)OH（1）羧酸）羧酸-三氟乙酸混合酸酐三氟乙酸混合酸酐适用于位阻较大的羧酸的酯化。适用于位阻较大的羧酸的酯化。RCOOH(CF3CO)2ORCOOCOCF3CF3COOHR COOCF3COHR COHOCF3COR CO HO COCF3-CF3COOHR COR1OH-HRCOOR1COOHt-BuOH(CF3CO)2Or.t.,20minCOOBu-
12、t(95%)（2）羧酸）羧酸-磺酸混合酸酐磺酸混合酸酐RCOOHTsCl/Py0oCRCOOSOOCH3R1OHRCOOR1TsOHRCOOR1=AcO(88%)AcO(80%)PhOONO2(98%)（3）羧酸）羧酸-磷酸混合酸酐磷酸混合酸酐RCOOHONOPONOOCl-HClRCOPNOOOO2R1OHr.t.RCOOR1RCOOR1=OCH3COOC2H5OCH3NNNNCOOC2H5CHCH3COOCH3(99%)(97%)(97%)4.酰氯为酰化剂酰氯为酰化剂 酰氯是活泼的酰化剂，反应能力强，适于位阻大的醇酰氯是活泼的酰化剂，反应能力强，适于位阻大的醇羟基酰化。多用碱催化。羟基酰化
13、。多用碱催化。RCOClR1OHRCOOR1HCl反应机理：RCOClNNCORClR1OHR COORNHRCOOR1NHClCOClCOOC(C2H5)3LiOC(C2H5)3THF/己烷,1h(94%)OHOHBzClTMEDA/CH2Cl2-78oC,2hOHOBz(99%)Bu-tOHBu-tClClOODMAP/AlCl3refluxBu-tOBu-tOOClAlCl3Bu-tOBu-tOO(90%)RCOClNCH2PhNCH2PhROCEt3NNCHPhROCEt3NHClRCOOHR1OH(RCO)2ORCOOR1R=Ph-R=Ph-CHCHPhR=R1=R1=R1=CH3-
14、Ph-CH3-(84%)(97%)(77%)CH3CH3H3CCOCl(C2H5)3COHAgCN/HMPA30minCH3CH3H3CCOOCEt3(92%)位阻大的酯，加入氰化银可是反应得到较好结果位阻大的酯，加入氰化银可是反应得到较好结果。PhOHOHPhCOCl0.01mol(CH3)2SnCl2/K2CO3r.t.,12h (95%)PhOHOCOPhPhOCOPhOH(90%)(5%)PhOHOHBu2SnO/TolrefluxPhOOSnBu2PhCOClr.t.,1hTMSClr.t.,12hPhOCOPhOTMSPhOTMSOCOPh(98%)(2%)OHCOOEtOHOAc
15、COOEtOHOHCOOEtOAcMeC(OMe)3/TsOH1hH2O30min(97%)(RCOHal (RCO)2O RCON3 RCOOR RCONR2 RCOOH RCOR1.羧酸为酰化剂羧酸为酰化剂RCOOHRRNHRCOO.H2NRRR COOHNRRHRCONRRH2OR COOHN C NNHC NRCOOR COO CNNHR COO CHNNH.RCOORNH2NCORCONHRCONHRNHCONHHRCOHORNCROONRRNH2RCNHRORNHCOHOBoc-L-Thr L-Phe-C3H7-i n-C3H7NC Boc-L-Thr-L-Phe-C3H7-i(8
16、3%)CHCl320oC,20hRCOOHRNH2NNNOPO(OEt)2Et3N/DMFr.t.20minRCONHRCbzNHHCCH2PhBocNHHCCH(CH3)2CbzHNHCCH2PhR=CH2CH2COOEt(95%)HC COOMeCH2OH(96%)HC COOMeCH(CH3)2(96%)R=1.羧酸为酰化剂羧酸为酰化剂2.羧酸酯为酰化剂羧酸酯为酰化剂RCOORRNH2R COORNH2RR COHORNHRRNH2R COONHRRRNH3RCONHRRO反应机理：PhCH2COOCH3NSOH2NCH2OAcCOOHBBr3r.t.,5hNSOPhH2COCHNCH2
17、OAcCOOH(67%)t-BuOOCCHCH2COOC6F5NHFmocPhH2CCHCOOHNH2t-BuOOCCHNHFmocHNCHCOOHCH2PhOEt3N/DMFr.t.,10min (77%)ROONOOH NRHRNHROHONOOR C O RONNNNNNClNOONOONOOMe2NMe2NO NN NBF4ROONNRNH2FeCl3或 CuCl2r.t.RCONHRNNHORRC15H31-C15H31-t-C4H9-t-C4H9-Ph-PhCH2-FeCl3CuCl2FeCl35min5min30min(87%)(94%)(85%)R=BocHNH2CCOOCCH
18、2CH3HOCH2CH2NH2AcOEtr.t.3hBocHNH2CCNHCH2CH2OHO(90%)3.酸酐为酰化剂酸酐为酰化剂反应机理：(RCO)2OHNRRRCOCROONHRRR CONHRRO CORRCONRRRCOOHOOOPhH2CCHCOOHNH2Tol,2hNOOHC COOHCH2Ph(95%)(1)羧酸羧酸-磺酸混合酸酐磺酸混合酸酐RCOHOTsCl/K2CO3/TEBA40oC,560minRCOTsORNH2ROHreflux,5120min(80%88%)40oC,10minRCNHRORCORO(77%95%)(2)羧酸羧酸-磷酸混合酸酐磷酸混合酸酐EtOPOE
19、tOBr(Cl)PhPOPhClON PNOOClOOEtOPOEtOCNPhOPOPhON3(DPP-Cl)(BOP-Cl)(DEPC)(DPPA)PhCHCOOHNHCbzNSCOCH2COPhOOH2NHHDEPCr.t.,2hNSCOCH2COPhOONHHHCOHCNHCbzPh(100%)(3)羧酸羧酸-碳酸混合酸酐碳酸混合酸酐RCOOHClCOOREt3NRCOOCOORRNH2RCONHRROHCO2BzLLeuOHClOBu-iOGlyOEtNOCH3/THF-15oC,4minBzLeuGlyOEt(93%)4.酰氯为酰化剂酰氯为酰化剂RCOXRNH2RCONHRHXNHO
20、ONOOH3CH2COCNaH110oCCH3CH2COClr.t.,1h(100%)COClNH(CH3)2CON(CH3)2(89%)(H3C)2HCH2CCHCOOHNHCbzNNNFFFPyr.t.34h(80%)(H3C)2HCH2CCHCOFNHCbzH3CCHCOOMeNH2/NOCH325oC,4h(H3C)2HCH2CCHNHCbzCNHCHCOOMeCH3O(95%)5.酰胺及其他羧酸衍生物为酰化剂酰胺及其他羧酸衍生物为酰化剂H2CCOOHNHCbzHOCH2HCNH2COOHNN C NNO/THFHOCH2HCNHCOCH2NHCbzCOOHr.t.(83%)RNOSS
21、RRNHONRSSNHRRCH2Cl2r.t.RCONRRHNSSRCONRR=NCC8H17O(97%);PhH2CONHONNH(98%)NOCH3Ph(100%)C15H31NONOH;(95%)NHCOOHPhH2CONOOOEt3Nr.t.24hNCOOHCOOCH2Ph(93%)ArNOOORNH2Cp2ZrCl2/THF25oCArNHRO(80%98%)Ar=Ph-,4-CF3C6H4-,3-ClC6H4-,4-ClC6H4-,4-MeOC6H4-;Cp=环戊二烯基RNONNNH3.H2O/EtOH/THFr.t.,24hRNH2ORNHRORNRRORNH2/THFr.t.,
22、4hRRNH/THFr.t.,4h(72%100%)(70%100%)(40%100%)二、芳香胺的二、芳香胺的N-酰化酰化H3CONH2(CH3CO)2OH3CONHCOCH3(90%)NH2CH3COClCH3COONaNHCOCH3(99%)NH2NHCOCH3NH3CCOCH3NHCH3Ac2OCH3IH2OCH2NH2H2NCH2NHAcH2NCH2NH2AcHNAc2OpH 4.15Ac2OpH 11.25(84%)(85%)SCH2COOHH3CH2NBOP-Cl/Et3Nr.t.1hSNHH3CO(96%)HONH2NNNNCOCH3THFHONHAc(95%)COOHNNNO
23、OONNNPyr.t.,1hNNNOPhOHONH2r.t.,1hHONHCOPh(94%)NHCH3NO2Ac2O/H2SO4NO2NCH3COCH3(73%)第三节第三节 碳原子上的酰化反应碳原子上的酰化反应一、芳烃的一、芳烃的C-酰化酰化1.Friedel-Crafts酰化反应酰化反应RCOZCORHZLewis AcidZ=Hal,RCOO-,RO-,-OH（1）反应机理：RCOClAlCl3RCO AlCl4RCOCORHAlCl4CORHAlCl4（2）影响因素1酰化剂(H3C)3CCOClAlCl3/PhH(H3C)3CClOAlCl3COAlCl4AlCl3C(CH3)3HCH
24、3OCH3ClO/AlCl334hCH3OCH3OAlCl3OH3COCH3OCH3OHCH3OOAlCl3AlCl3O(91%96%)OClnAlCl3Onn=2(90%)n=3(91%)n=4(50%)C(CH3)3C(CH3)3COClAlCl3/CS2OCH3CH3OOOH3CAlCl3(82%)CH3CH3CH3COOHOPd-C/H2/HOAcCH3CH3CH3COOHPPACH3CH3OCH3(95%)(94%)COClCH3CH3CH3CH3COPhCF3SO3H(82%)AlCl3(26%)H3CCH3COOHCF3SO3H25oC,2hH3CCOCH3(97%)2被酰化物的
25、结构影响HCClHCEtCOClOMeMeOOEtOMe OEtAlCl3/Py(71%)(13%)CH3CH(CH3)2CH3COClAlCl3/CS25oC,3hCH3CH(CH3)2COCH3(50%55%)OMeMeOMeOOMeCH3COCl/AlCl3(64%)OOHMeOMeOOMeHOOCOOPCl5AlCl350oC(63%)CH3H3CCH3CH3COClAlCl3COOHCH3H3CCH3COCH3COCH3(71%)3催化剂：Lewis 酸 AlCl3、BF3、SnCl4、ZnCl2 质子酸 HF、HCl、H2SO4、H3BO3、HClO4、CF3COOH、MeSO3H
26、、CF3SO3H、PPANCOOC2H5C2H5OOCBBr320oC,15minNC2H5OOCO(88%)OHOHC CH3Ocat.Hf(OTf)4/CH3COCl100oC,6h(90%)OSeMeOCuOTfr.t.15minOO(100%)4溶剂：CH3PhCOClAlCl3CH3CH3COPhCOPh溶剂 对位/邻位二氯甲烷 9.3苯甲酰氯 9.6硝基苯 12.72.Hoesch反应反应CNRCNHRCNHRClHOOHHOHOHCNHRClOHHOCNH2ClR-NH4ClOHHOCORNH2ClCH2CH2CH2CNBCl3/GaCl3/PhCl100oC,20hHCl/H2
27、ONH2O(CH2)3Cl(87%)Cl2CHCNAlCl3NH2.ClCHCl2H2OCOCHCl23.Gattermann 反应反应HCNHClAlCl3H CClNHArH/AlCl3-HClArCHNHH2O/HClArCHONH4ClOHCHOOHZn(CN)2/HCl/AlCl3CH3H3CCH3CH3H3CCH3CHOZn(CN)2/HCl(85%)(75%81%)ClTMSCN5%SbF5/95%TFSA20oC,10minClClCHOCHO(25%)(75%)(93%)H3CCOHClCu2Cl2/AlCl3H3CCHO(85%)4.Vilsmeier-Haauc反应反应R
28、NRCHOPOCl3RNRC OHClPOCl2NR2NR2ClHCHClNRR-HNR2HCClNRRH2ONR2CHO(H3C)2NDMF/POCl3(H3C)2NCHO(84%)NHCOOC2H5PhNCH3CHOPOCl3heat,1hNHCOOC2H5CHO(99.5%)YOCH2RDMF/POCl3NMe2OCH2RYOYR(3%78%)R=-(OR)2,-CN,-COPhCl5.Reimer-Tiemann反应反应CHCl3OHCCl3:CCl2-ClO:CCl2OHCCl2OCHCl2OHOCHOOHOHOHCHOCHO(20%35%)(8%12%)CHCl3/10%NaOH5
29、5oC,3hOHNaOH/CHCl3/环糊精60oC,20minOHCHO(65%)NHO50%NaOH/CHCl3NHOCHO(32%)二、烯烃的二、烯烃的C-酰化酰化RCOClRHCCH2AlCl3/CHCl3RCOCH2CHClRPhCOONa or PhNEt2ROCHCCHROOOPPA/MeSO3H60oC,12h(94%)COClBF3/Et2OCO(53%)BrOAlCl3/CH2Cl2-78oCOO(72%)SC4H9-nCH3COClSC4H9-nCOCH3Clay-K10-Al3+(72%)COCl/AlCl3/CH2Cl2PhOCC2H5ClC2H5PhOCC2H5C2
30、H5ClEtEtO-40oC(80%)(12%)(8%)CHCH2Me3SiRCOCl/Lewis AcidR COHCSiMe3CH2R C CHOCH2SiMe3CH3COClAlCl3/CH2Cl2O(88%)SiMe3COClOTiCl4/CH2Cl20oC(84%)SiMe3PhPhCH2COCl/AlCl3PhOPh(86%)SiMe3MeCOCl/AlCl3SiMe3ClOO(60%)ClOSiMe3AlCl3,0oCO(90%)C C C2H5C2H5三、羰基化合物三、羰基化合物位的位的C-酰化酰化1.活性亚甲基化合物的活性亚甲基化合物的C-酰化酰化RCOClYH2CXBYRO
31、CHCXY,X=COOR,CHO,COR,CONR2,COO ,CN,NO2,SOR,SO2RCOCH3H2CCOOC2H5BCOCH3HCCOOC2H5PhCOClPhCHC COOC2H5COCH3ONH4Cl/H2OPhCOCH2COOC2H5 NH4OAc(68%71%)H2CCOOEtCOOEt1)MgCl2/Et3N2)NClClONClClClOOEtOOOEtDMSO/H2O150160oC,2hNClClO(92.8%)COClNO2C2H5OMgCH(COOC2H5)2COCH(COOC2H5)2NO2(82%88%)H2CCOORCOOH2RMgXOROOOMg2RCOC
32、l orNNROCRCOCH2COORH2CCOOEtCOOKMgCl2/Et3NRCOCl/CH3CN0oC up to r.t.RCOCH2COOEt(83%94%)PhCOOHXH2CYDEPC/Et3N/DMFr.t.PhC CHXYOX=CNY=COOC2H5(93.4%)X=HY=NO2(85.5%)X=CNY=CN(92.8%)X=COOC2H5Y=COOC2H5(96.8%)2.酮及羧酸衍生物的酮及羧酸衍生物的位位C-酰化酰化RCH2ZROROHR CHZRCOYRC CHRZOYYRCHC RZORORC C RO ZZ=;Y=NN-CN-COOR,-COR-OR,-Cl(1
33、)Claisen反应和反应和Dieckmann反应反应RCH2COOEtEtOEtOHRCHCOOEtRH2CCOEtORH2CCOCHRCOOEtOEtEtORH2CCOCHCOOEtREtORH2CCOC COOEtRRH2CCOC COOEtRH3CCHCOOEtH3CBH3CCHH3CCOCCH3CH3COOEtBH3CCH3CCONaCCH3CH3COOEtB=EtONa(0%);B=Ph3CONa (60%)PhCH2COOEtCOOEtCOOEtEtONaPhCHCOOEtCOCOOEt-COPh CHCOOEtCOOEt(80%85%)COOEtCOOEtCOOEtCOOEtE
34、tONa(91%)COCOOEtCOOEtCOOEt12mol/LHCl(83%)COCOOHCOOHH3COH3COCOOEtEtONa/HCOOEtH3COH3COCOOEtCHO(69%)PhCH2COOEtEtOCOEtOEtONaPh CHCOOEtCOOEtEtOH(86%)OCOOCH3CH3CH2CH2COOCH3MeONa/PhHOCCHOCH2CH3COOCH3(70%)CH3COOCH3LDAH2CCOLiOCH3CH3(CH2)12COClCH3(CH2)12COCH2COOCH3(83%)COClMeCOOEt/LDACOOEtO(86%)NCOOEtCOOEtMeC
35、OOEtNaH/PhHNCOOEtCOOEtMeOHt-BuOK/PhMe-25oCNCOOMeMeOHEtOOCNCOOEtCOOEtMeOH(28%)(58%)OCOOMeCOOMeMeOOBzlBzlO(Me3Si)2NNaOCOOMeMeOOBzlBzlOO(77%)NMeCOOMeCOOMeNaH/PhHNOCOOMeMe(86%)COOEtCOOEtbaseOEtOOCOCOOEt(80%)OOOHCOOMeCOOMet-BuOK/DMSOOOOHCOOMeO(88%)OOOOOMeOOCt-BuOK/PhHOOOOOOHHHH(91%)Dieckmann Reaction（2）酮
36、、腈的）酮、腈的位位C-酰化酰化RCH2CORBRHCCRORCOORBRCOHCRCORRCOCRCORRCOCRCORCH3COCH3CH3OCH2COOCH3CH3ONa6065oCH3COH2COCHCCCH3ONaOt-BuHCOOEtNaH25oC,5hOt-BuCHO(95%)OEtOCOEtONaH/PhH/AcOH/H2OOCOOEt酰化机理：酰化活性：OH3COH3CCOOEtLDACNCOOEt/THF/HMPT(86%)RCH3ORCH3MeOOMeCl3CCOCl/Py/CH2Cl2030oC ,12hROMeCCl3O(85%96%)OSiMe3PhCH3CH3CO
37、Cl/BiCl3-ZnCl2r.t.,40minPhCH3OOCH3(93%)OOLiOOLDA/THF0oCn-PrCOCN(94%)H3CCH2C2H5OBF3/AcOHH3CCH3OOC2H5(57%)OCH2CH2COOCH3NaOCH3/Et2OOO(90%)PhCH2CNEtOOEtOEtONa/TolPhHCCOOEtCN(78%)NHNCNCOOEtNaH/PhHNHNOCN(88%)H3CORH2COR2HCO（3）烯胺的）烯胺的C-酰化酰化NCHCl3COClCH3HCl,H2OCOOCH3C CNC CNOOHNClay-KSFreflux,24hPhCOClOPhO(6
38、4%)i-PrCH3ORNH2HNi-PrCH3RLDA/THF10oCRCOBt-78oC,overnightNHRi-PrRO(65%90%)H3CNH3CCHCCH3CH3PhNC OCHCCN(H3C)2NPhOH3CCH3H2OH3CCH3CCHOCONHPh四、四、“极性反转极性反转”在亲核酰化反应中的应用在亲核酰化反应中的应用NHRH2CXN CH2RCHCOC OCOCH CO正常特征反应：极性反转情况：PhCHOMPhCOMRXPhCORMXPhCOCOPhMClRCOClRRORRO1，2-加成1，4-加成RHOCOPhRRROHOPh1.将羰基化合物转化成将羰基化合物转化
39、成1,3-二噻烷衍生物二噻烷衍生物SHSHRCHOHSSRHn-BuLi/THFSSRRXSSRRH2O/HgORCROSSRRCOClRCHOCHCH2ORO/THF1)2)H2OSSRCORR COCORSSRCH ROHR COCHOHRSSRCH2HCOHRR COCH2CHOHROHCOREtSCH2SEtO,SSRHSSSRHPhSSPhRSSRRHSS RHMeMe,1，3-二噻烷类似物及其应用：RR SSOn-BuLi/EtIRR SSORR SSORR SSOEtCH2CH2COOEtH2CCHCOOEt(95%)Lin-BuLi/THF0oC,20minEtCCH2CH2C
40、OOEtOH2O/HgCl2SSHLiCl(CH2)3I/THF-50oCSSH(CH2)3Cln-BuLi-70oCSSH2O/HgCl2O(83%)(61%)(60%)(100%)OEtOEts-BuLi/t-BuOK2hi-PrCHO-95oC,2hCHOEtPr-iOHH2OOCH Pr-iOH(90%)2.将羰基化合物转化成将羰基化合物转化成-氰醇衍生物氰醇衍生物OCHOCNOOCNOOHCNi-PrIHOPr-iOOEtCHMeOCHMeCNOEtCHMeOCMeCNH3CCC6H13-nOn-C6H13BrH3O(75%)3.将羰基化合物转化成苯并咪唑醇衍生物将羰基化合物转化成苯
41、并咪唑醇衍生物NNMeMeHINaHNNMeMeArCHONNMeMeCOHArRClNNMeMeCOHArRNNMeMeCOArRArCRONNMeMeNNClCH3CHOCl(BM)BM/DMFr.t.10minNNCH3ClO(93%)ClN C ClPhCHONO2NNMeMeHI/NaHr.t.1hClN C CONO2Ph(87%)4.用硝基前体为屏蔽羰基的用硝基前体为屏蔽羰基的C-亲核酰化亲核酰化C2H5CH2NO2BC2H5CHNO2H3C COCHCH2C2H5HCNO2CH2CH2COCH3TiCl3pH 6C2H5COCH2CH2COCH3(85%)5.将羰基化合物转化成
42、烯醇醚衍生物H2CCOCH3LiO1，2-加成H2CCOCH3HOH2O/HH3CCOHO(86%)O1，4-加成（67%）H2C COCH32CuLiOCOCH3CH2O3/MeOH(73%)稀 HCl(80%)COOCH3OCOCH3OH2CCSEtHH2CCSEtLiH2CCSEtC8H17-nH3CCC8H17-nO(90%)n-C8H17BrH2O/Hg2+OH3Cs-BuLiOH3CLiOH3CBrn-BuLi/THFOOHOAc/H2OO(40%45%)EtOH/NaOH第四节 有机金属化合物在C-酰化中的应用一、有机金属化合物和酰化剂的反应R COYRMgXRCRORMgXH2
43、OR COHRRY=Hal,OCOR,OR,NR2,O MRNOMeMeORM/THFONMeOMeRRMH3ORROPhNOMeMeOCH3MgBrTHF0oC,1hPhCH3O(93%96%)NOArNOMeMeOt-BuMe2SiORMgX(45%99%)NOArROt-BuMe2SiO(Ar=OMe)活性硫醇酯为酰化剂：RSONRMgBrRSONMgRBrORRSNMgBrRROOHOOSHSHBF3.Et2O(97%)OHOSSPh3P/NS2SOSSNRCH2MgBr/THFH2O0oCr.t.(93%)OSSRH2O/CH3COCH3,4h(99%)OORNaOH/EtOH,6h
44、(81%)ORcis-茉莉酮NOORMgBrNOOMgBrREt2O0oCRONOMgBr(98%)EtNONMeRMgBr/THF-780oCEtNONMeRMgBrHClRO(75%94%)n-C6H13MgBrMeCOClTHF-78oCn-C6H13COCH3(93%)RMgXHC(OC2H5)3R CH(OC2H5)2HR CHO有机锂试剂参与的反应：PhNOOMeMePhCCLiTHF20oC,1hPhCOCPh(90%)RORORLiROXRTMS-ClROSiMe3XRH3ORROR=H or EtX=OEt or OTMSOOOMeOMeLi/THFOOHH(95%)OMeO
45、MeOLiOOHOOOHOMeLi/THF-78oC-78oC有机铜试剂参与的反应：MeOClOOMeOOO(96%)(CH3)2CuLi/Et2O-78oCBr(H2C)5OON0.7mol n-Bu2CuLi/Et2OBr(H2C)5Bu-nO(90%)-78oC,0.5hINHBocCOOBnZn/Cu60oCIZnNHBocCOOBnEtCOCl/(Ph3P)2PdCl2NHBocCOOBnEtO(83%)IZn/Cu/PhH/DMFCuICOCl/Pd(PPh3)4O(100%)有机金属试剂与腈类化合物的反应：R CNRMgXR C RN.MgXH3OR C RNHHClR C RONH4ClCH3CH2CNPhMgBrPhCH2CH3O(93%)CNPhMgBr,4hCPhNHHOAc/H2OCPhO(85%)本 章 小 结n掌握羧酸、酸酐、酰卤及酯作酰化剂和醇的酰化作用n掌握羧酸、酸酐、酰卤及酯作酰化剂和胺的酰化作用n掌握F-C的酰化、Gattermann反应n熟悉羰基位碳酰化和极性反转
