1、 Chapter 17 醛酮醛酮 Chapter 18 烯醇，烯酮，烯胺烯醇，烯酮，烯胺 Chapter 19 羧酸羧酸 Chapter 20 羧酸衍生物羧酸衍生物 Chapter 22 胺胺 Chapter 23 含氮芳香化合物含氮芳香化合物以及前面各章Ozonolysis of Alkenes（不推荐在合成中使用）（不推荐在合成中使用）CCO3COOCHydration of AlkynesCCH2OH+H g+CCHO HCCHOH醛酮的制备：Chapter 17 醛酮醛酮 O R COCO HCO HO O R RCOClAlCl3COROH醇的氧化醇的氧化Friedel-Crafts
2、 酰基化酰基化RCO HR R O R N o reacti on思考：无思考：无AlCl3 生成什么？生成什么？Gattermann-Koch 反应反应:+CO +HClAlCl3,CuClCHO+HClCH3CH3 MnO2H2SO4CH3CHO芳烃的氧化：芳烃的氧化：Fehling Test:Tollens Test:(Red)R RC C H HO O +C C u u +N Na aO OH H +H H2 2O OR RC C O OO O N Na a +H H +C C u u2 2O O2 2+R R C C H H O O +2 2 A A g g(N N H H3 3)2
3、 2 O O H HR RC C O OO O N NH H4 4 +N N H H3 3 +H H2 2O O +A Ag gN uCOR1R2HCOR1R2HN uCOHHCOR1HCOR1R2被进攻的羰碳的反应活性被进攻的羰碳的反应活性:原因：原因：1.位阻位阻 2.取代基的给电子效应取代基的给电子效应醛酮参与的反应：醛酮参与的反应：常见亲核加成的亲核试剂：常见亲核加成的亲核试剂：含碳含碳 HCN,RM,MCCH（格氏试剂，炔钠）（格氏试剂，炔钠）含氮含氮 NH3,RNH2,R2NH,H2N-Y 含氧含氧 H2O,ROH（醛酮的水解，羰基的保护）（醛酮的水解，羰基的保护）含硫含硫 RSH
4、,NaHSO3（鉴别醛酮类化合物）（鉴别醛酮类化合物）CORHCRHO N aSO3H某醛亚硫酸氢钠加成物SOH OO N aCRHO HSO3N aHCN+RCOR CN CR O HR加热氰基才变为羧基加热氰基才变为羧基CH3CH2CCH3NaCN HClCH3CH2CCH3H2SO4CH3CH2CCH3COOHCCH3H3CH2COOHCNOHCOOHAldehyde or Triphenylphosphonium Triphenylphosphine Ketone ylide(磷叶立德)oxideReaction type:Nucleophilic Addition then Elim
5、ination Ph3PCH2O +DMSOCH2RCOR+RNH2RCNRRPrimary amineImineCH +CH3NH2OCHNCH3NH3RNH2NH2NH2NH2OHNH2NHCNH2ONH2NHArAmmoniaPriary amineHydroxylamineHydrazineSemicarbazideArylhdrazine与一级胺反应R RC CH H2 2C CR R +R R 2 2N NH HR RC CH H2 2C CR R R RC CH HC CR R N NR R 2 2O OO OH HN NR R2 2 O O+H HN NC C6 6H H6 6
6、C CH H3 3H HO O3 3S SN N烯胺的烷基化和酰基化烯胺的烷基化和酰基化NR-XR-C-XONNRROH2OHRROOO与二级胺反应O OC CH H3 3C CH HO O1 1.3 30 0%N N a aO O H H,C C H H3 3O O H H2 2.H H3 3O OO OC CH H3 3C CH H2 2O OH H+H HC CO O O OH H+C CH H2 2O OC Cl lC CH HO O1 1.5 50 0%N N a aO O H H2 2.H H3 3O OC Cl lC CH H2 2O OH HC CO OO OH HC Cl l
7、+RCOR RCOO O H+RCOOR +R C O O H原子插在位阻大的一边。R RC CH H (R R )O O H H R RC CH H2 2H H (R R )lClemmensen Reduction(acidic conditions)Zn(Hg)in HCl reduces the C=O into-CH2-lWolff-Kishner Reduction(basic conditions)NH2NH2/KOH/ethylene glycol(a high boiling solvent)reduces the C=O into-CH2-以上方法不还原以上方法不还原C=C
8、,C C 或-COOHCHHOHCHHO HCR HOR CHHO HCR R OR CR HO H+Li A l H4N aB H4C CH HO OO OC CH H3 3H HO O1 1.A Ag g2 2O O,N N a aO OH H,H H2 2O O2 2.H HC Cl lC CO OO OH HO OC CH H3 3H HO O酸催化的机理R R C C H H2 2C C R R O OH HO OH HH HF Fa as st t+R R C C H H2 2C C R R +O OH HO OH HH HO OH HH HR RC CH HC CR R H HO
9、 OH H+S Sl lo ow wR RC CH HC CR R +O OH HH HO OH HH HR RC CH HC CR R H HO OO OH H+S Sl lo ow wR RC CH HC CR R +H HO O H HO ORC HC RORC HC ROR RC CH HC CR R O OO OH HH H+F Fa as st tR RC CH HC CR R +H H O OO O H HC H3C C H2C C H3K =4C H3CC H C C H3O HOOOC H2C C H2C C H3O HO不稳定不稳定-Diketones（对称）H2CC C
10、H2C H3O HC H3C C H2C H3OC H3CC H C H3O H(不对称)多取代热力学稳定多取代热力学稳定少取代动力学不稳定少取代动力学不稳定R RC CC CO OR R +X X2 2R RH HR RC CC CO OR R +H H X XR RH Hx xCOC HRR COC H2RCOC H3RCOCHR R X2O H-RCOCXR R HO H+X-+醛酮的醛酮的 卤代卤代C CO OC C H HC CO OC C H H 2 2 C CO OC C H H3 3 Haloform 反应（鉴别甲基酮）反应（鉴别甲基酮）RCOCHHH3 I24 OH-RCOO
11、HOH+CHI3+3IRCH2CHONaOHRCHCHORCH2CHOHCOCHCHROHCH2RDehydrtionHCOCCHRCH2R(heat)O OH HH HC CH HO OH HC CH H +H H2 2O OO OR RR RH HH HC CH HO OR RH HC CH H2 2O OR RH HC CO OR RC CH H2 2R RO OH HH HH HC CO OR RC CH H2 2R RO OH HH HH HO OH H-O OH HH HC CO OR RC CH H2 2R RO OH HH HH H O OH HH HC CO OR RC CH
12、 H2 2R RO OH HH HH HF Fa as st tH HC CO OR RC CH H2 2R R +O OH HH HH H2 2O O机理（分子内同理）机理（分子内同理）H HC CO OR RC CH H2 2R RO OH HH HS Sl lo ow wH HC CO OR RH HC CC CH H2 2R R+O OH HH H3 3C CC CC CH H3 3O OC CH HO O+N Na aO OH HO OH C H +O(C H3)2C H C H2CHO K2C O3H2O-Et2O(C H3)2C H C HC H2O HCOH何时脱水？（1）产物
13、在羰基和羟基间要有一个 -H（2）共轭（3）加热（4）无水环境 a,b 不饱和羰基化合物不饱和羰基化合物C CC CC CO OC CC CC CO OC CC CC CO O34OHNuOHNuDirect or1,2-AdditionOHNuConjugate or1,4-Addition12快 稍慢 弱碱：RSH，CN-，R2CuLi，烯醇强碱：RLi,RMgX,LiAlH4CH2CHCORH2CCHCORRSHRSH1.R2CuLi2.H3O+KCNH2CCHCORNCHH2CCHCORRHRCOCRRH2CCHCORCHCRRORMichael AdditionOC H3O+C H2
14、C HCC H3O K O HC H3O HOC H3OC H2C H2C C H3OOO+N aO HO+H2ORobinson 成环成环OC H3OC H2C H2C C H3OA lO C(C H3)33 C6H6,H eatOC H3O HON ot isolated2-M ethyl-2-(3-oxo-b utyl)-cycloh exane-1,3-d ione-H2OOC H3O8a-M eth yl-3,4,8,8a-tetrahyd ro-2H,7H-nap h thalene-1,6-d io neO OC CH H3 3+L Li iA Al lH H4 41 1.E E
15、t t2 2O O2 2.H H2 2O OO OH HC CH H3 3O OC CH H3 3+H H2 2O OH HC CH H3 3P Pd d-C C3 3-M M e et th hy yl l-c cy yc cl l o oh he ex xa an no ol l3 3-M M e et th hy yl l-c cy yc cl l o oh he ex x-2 2-e en no on ne eH H3 3C CO O1 1.L Li i,N NH H3 3(l l)2 2.H H2 2O OH H3 3C CO O羧酸的制备羧酸的制备RCOXRRCOCORCOO R
16、RCON H2OH2ORCOO HBrNaCNCNH+H2OCOOH腈的水解（制备增加一个腈的水解（制备增加一个C的羧酸）的羧酸）格氏试剂和格氏试剂和CO2 反应反应RC O O H O O =C r2O7-2 or M nO4-2/H2SO4/H eat烃基取代的苯的氧化烃基取代的苯的氧化羧酸生成羧酸衍生物H H O O C C H H2 2C C H H2 2C C H H2 2C C O O H HO OO OO OR C O O H +Li A l H4CO HR +H2OHHR R C C H H2 2C C O O H H +X X2 2O OP PX X3 3R R C C H
17、H C C O O H H +H H X XX XO OCH3CH2CH2CH2COOHBr2PBr3CH3CH2CH2CHCOOH K2CO3H2O,HeatCH3CH2CH2CHCOOHBrOH羧酸的还原羧酸的还原羧酸的羧酸的卤代卤代CHCOOHCOOHCH2COOH+CO2二羧酸的脱羧二羧酸的脱羧RClOROOR1OROOR1ROHORNH2OROO=亲核试剂进攻时，羰基的活性：比如水解RCOXRRCOCORCOO R RCON H ROH2ORCOO HR O HRCOO HR N H2RRCOCORCOO R RCON H ROH2OR O HRCOO HR N H2NOOOO Et
18、OOO HO EtOOC lO EtOOC lB rEtO2CC O2EtB rEtO HSO C l2B r2EtO HRCOO R RCON H RH2OR O HRCOO HR N H2RCOO R B aseR R C C O O R R +H H2 2O OO OR R C C O O O O H H +R R O O H HH HR RC CO O R R O OH HO OH HH HR RC CO O R R +H H2 2O OO OH HR RC CO O H HO O R R R RC CO O H HO O R R R RC CO OO O R R H H酯的水解（机理
19、）酯的水解（机理）R RC CO O R R O OH HO OH HH HR RC CO O R R O OH HO OH HH HR RC CO O R R O O H HO OH HH HR RC CO O R R O O H HO OH HH HO O H H+H H3 3O OR RC CO O R R O O H HO O H HO OH HH HH HR RC CO O R R O O H HO O H H H H+H H2 2O OR RC CO O R R O O H HO O H H H HR RC CO O H HO O H H+R R O O H HO OH HH HR
20、 RC CO O H HO O+H H3 3O OH HR RC CO O H HO OC H3COO C(C H3)3C H3CO HO C(C H3)3C H3CO HOC H3CO HO C(C H3)3+C(C H3)3(C H3)3CO H2(C H3)3CO HH+H2OH+RCOORN a无 水 E tO HR C H2O H +R O H酯的双分子还原酯的双分子还原RCOORRCOOR二甲苯RCONaRCONaRCORCOHAcyloin condensation偶姻缩合NaH2O2R Li2R M gXR COO R R CO HRR2.H3OOO1.2C2H5MgBr/TH
21、FOHEtEtOHCCC6H5C6H5HHC6H5C HC H2C6H5OCOC H3CCC6H5HHC6H5+(主)5 0 0CH3CHOCH2CH2CH3COCH3500CH2CHCH2CH2CH3CH3CHCHCH2CH357%43%趋向于消除酸性较强，空间位阻较小的 HRCOOH+HOH+RNH2heatRCONHRacidRCOOCOR+RCOOHR2NHRCONR2+acid anhydride RCOOR+ROHRNH2RCONHR+esterRCONH2RCN+H2OH+or OH-nitrile=acid chlorideR2NH2+Cl-+RCONR2R2NH+2RCOCl
22、RCOOH+RNH2RCONHRRCH2NHR(1)(2)H2OLiAlH4H2OH+or-OHBr-,OH-RNH2+CO2POCl3(or P2O5)RCN(NaOBr)酰胺参与的反应酰胺参与的反应RCONH2RCNPOCl31 amideRCN+RXNaCNNa+X-alkyl halide+ArNN+CuCNArCNN2diazonium salt RCORHCNKCNRCRHOCNaldehyde or ketonecyanohydrin=RCONH2RCH2NH2(1)(2)LiAlH4H2OH+or-OHRCNH+or-OHH2ORCOOHH2ORMgXRCNRMgXH3O+RC
23、ORNCH3CH3CH3s p3 h y b rid iz e d亲核性亲核性和和碱性碱性（N上连有给电子基可以增加碱性）上连有给电子基可以增加碱性）NH2NH2NH2NH2ONO2 RNO2RNH2RCNRCH2NH2RCNH2ORCH2NH2RCONHRRCH2NHRRCONR2RCH2NR2RCRNHRCRHNH2RCRNRRCRHNHRCCHNR2CHCH2NR2RCRONH3orRCRORNH2H2/Pt or LiAlH 4H2/Pt or LiAlH 4LiAlH 4LiAlH 4LiAlH 4H2/PtLiAlH 4orH2/PtLiAlH 4H2/Pt or LiAlH 4H
24、2/PtH2/Ptor Sn/H+(excess)C H3C H2C H2C H2C HC H2+(C H3)3NC H3(C H2)5N H2C H3IC H3(C H2)5N(C H3)3 IA g2OC H3(C H2)5N(C H3)3 O HHofmann 消除消除(C H3)3C C H2C N H2OB r2,N aO H H2O(C H3)3C C H2N H2B rC N H2OB r2,N aO H H2OB rN H23-B rom o-benzam i de3-B rom o-phenyl am i ne(87%)3,3-di m ethyl butanam i de2
25、,2-di m ethyl propan-1-am i neRCON H2 +B r2 +4 O HR N H2 +2 B r +C O3 +H2ORNCOH2O芳香胺芳香胺亲电芳环取代亲电芳环取代氧化氧化对二氨基联苯重排对二氨基联苯重排重氮化重氮化NH2Br2H2ONH2BrBrBrAniline2,4,6-TribromoanilineNH2(CH3CO)2OPyridineNH COCH3NH COCH3Br2BrH2OHClNH2Br+CH3CO2HNH2I2NaHCO3NH2INH2(CH3CO)2OPyridineNHCOCH3NHCOCH3COC6H5AlCl3C6H5COClNH2室温发烟 H2SO4NH2SO3HNHCOCH380NHCOCH3SO2Cl(1)RNH2NH2SO2NHR(2)HClClSO3HNH2MnO2H2SO4,20OONH2BrBrCH3CO3HCH2Cl2NO2BrBrNHNHNH2H2NH2NH2NH+70%30%N H2+H N O2 +H2SO4NNH SO4NNH SO4:N u+N u+N2COOHCH3HHO1.(CH3CH2)2O2.H3O机理要按步骤写机理要按步骤写D-A反应，醚的水解作业的合成题！
