2.1章羧酸衍生物ppt课件

1、 Chapter12 CarboxylicAcidDerivative RC O X RC O NH2(R) RC O ORRC O O C O R RCN acylhalide amide ester anhydride nitrile 一一.StructureandNomenclature (一一)Structure RC O L the general formula P- conjugation SP2 hybridization resonancehybride RC O L SP hybridization RC O LRC O L HC O N H H HC O N H H HC

2、 O N H H RC NRC N (二)、Nomenclature acylhalideamide H CC O Br 邻苯二甲酰亚胺 HC O N CH3 CH3 DMF HC H3C NH O O N,N-二甲甲酰胺3-对甲苯基烯丙酰溴 anhydridenitrile O C O H3C CN 乙腈 C 乙（酸）丙（酸）酐苯甲酸酐 O O C O CH3C O CH3 甲氧甲酰基 CN 氰基乙酰氧基 O CH3C O O C O CH3 C O NH2 C O Cl 氨甲酰基氯甲酰基 H3COOC 邻苯二甲酸二乙酯 O C O CH3H2C 乙二醇二乙酸酯- -甲甲基基- - -戊戊内

3、内酯酯 COOCH3 O O CH3 O C O CH3H2C OHC O RSO3HR OC O R ORC O R XC O RNR2C O R CNRHC O RRC O R OHROHArNR2RRO R ester 2 二二.PhysicalProperties 低级酰卤、酸酐：刺激性气味，气体低级酰卤、酸酐：刺激性气味，气体 低级酯：易挥发、香味低级酯：易挥发、香味 酰胺：固体甲酰胺、酰胺：固体甲酰胺、N-取代酰胺液体）取代酰胺液体） 酰卤、酯、酸酐酰卤、酯、酸酐:b.p.(nohydrogenbond) NH酰胺：酰胺：bp.,mp.COOH(hydrogenbond) N取代酰

4、胺：液体，取代酰胺：液体，bp.,mp.(nohydrogenbond) DMF 腈：极性大，腈：极性大，mp.,bp.(nohydrogenbond) IR C=O:18501630cm-1 1H-NMR -H:23COO-CH2-:3.74.1CON-H:58 三、三、ChemicalProperties (一一Nucleophilicreaction L LC O R Nu +Nu C O R Nu= H2O, ROH, NH3, RNH2 L= -X, -OOCR, -OR, -NH2(R) H3CC O Cl +HCl C19H39C O Cl H2O n- H3CC O OH H2

5、O dioxane C19H39C O OHn- +HCl (1) The hydrolysis of the acyl halides HL LC O R+OHC O R H2O+ 1. Hydrolysis +H2OO H3C H O O OH H3C H O O OH (2). Acid Anhydrides (3)Thehydrolysisofester OC O R 酰氧断裂 ROC O RR 烷氧断裂 acidorbasecondition BaseCondition(亲核加成亲核加成消除消除) OCC O H3C (R)-(+)-1-苯乙醇 EtOH-H2O + KOH OKC

6、O H3C CH3 H C6H5 CHO CH3 H C6H5 (R)-(+)-乙酸-1-苯乙醇酯 C-O断裂途径(两条） AcidCondition 1o,2o-酰氧键断裂酰氧键断裂 RC O OR H RC OH OR HOH RC OH OR OH2 RC OH OR OH H -ROH RC OH OHRC O OH H + Mechanism 叔醇酯：烷氧键断裂 acidity,mechanism + NH3 H2O RC O OH fast RC O NH2 + H RC OH NH2 RC OH NH2 OH2 RC OH OHRC OH NH3 OH + NH4 + KOH H

7、2O H3CC O OK 100oC NHC O2N OCH3 O CH3 NH2 O2N OCH3 base,mechanism (4). Amides (5).Nitrile-COOH OHH3O Mechanism R C N OHH or H2O R C O NH2 OHH3Oor R C O OH 活性顺序： R C O Cl 1011 R C O O C O RR C O ORR C O NH2 R C O NR2 R C O L 10-2 1071.0 NH2RORCOO Cl 醛、酮：亲核加成 羧酸衍生物：亲核取代 (二二)Alcoholysis R C O L HL HOR+

8、 + R C O OR （1）.AcylHalides Schotton-Baumann HCl Et2O + (H3C)3CC O Cl + Py + H3CC O Cl OH (H3C)3CC O ON (H3C)3COH C6H5N(CH3)2 H3CC O OC(CH3)3 + C 6H5N(CH3)2 HCl H3CC O O + H2SO4 +H3CC O OH OH H3CC O O 2 SO3H + C2H5OH O O O OC2H5 O O OC2H5 (2).AcidAnhydrides (3).Alcohols + PTS H3C C O OCH3 OH OH3C C

9、O +HOCH3 (4).Nitrile +HClH3CC N+HOC2H5CH3C(OC2H5)3NH4Cl H2CC O Cl OH bNaCN aNa2CO3 H2CC O CN ONa H2SO4 C2H5OH H2CC O CO2C2H5 OC2H5 + 3、Ammonlysis (1).Acylhalides + NaCl+ H2O C6H5C O Cl bNaCN NaOH HN + C6H5C O N (2).AcidAnhydrides O O O NH3 ONH4 O O NH2 H 300oC OH O O NH2 NH O O + (3).Ester OH O C2H5

10、OH NH2 CH3 OC2H5 OH O HN H3C + + +H2NNH2OC2H5CH3CH2C O +C2H5OHNHNH2CH3CH2C O + H2NOHOC2H5CH3CH2C O + C2H5OHNHOHCH3CH2C O (4).Amindes CH3NH2 NH2H3CC O NH3NHCH3H3CC O + (二二)、ReactionwithMetalAgents 1.GrignardReagents H3C C O Cl +CH3MgI FeCl3 -15oC H3C C O CH3 CH3MgIH3C C OH CH3 CH3 CN-CO RMgX CNR bH2O

11、 aC6H5MgBr CNMgXR R H2O C O RR CN C O 酰胺、酸酐 R2CuLi ketone n- X -CN C O ROR C O RX C O RNH2(R2) R2CuLi C O C4H9O(CH2)4C O Cl (CH3)2CuLi n- C O C4H9O(CH2)4C O CH3 2.R2CuLi LiAlH4 Hx+C O RX C O ROC CH2OHR O R LiAlH4 RCH2OH+ CH2OHR C O ROR LiAlH4 ROH+ CH2OHR CNR LiAlH4 CH2NH2R C O RNH2 LiAlH4 CH2NH2R (三

12、三)、Reduction 1.LiAlH4 2.RosenmundReaction Pd/BaSO4 H2,Pd-BaSO4 C O RX R=aliphaticoraromatic C O RH quinoline 3.CatalyticHydrogenationorChemical Agents Bouveault-Blanc ref. Na + EtOH C O C2H5OCH2CH=CHCH3 + CH3CH2CH2OH H2/CuO.CuCrO4 125oC/加压 COCH2CH=CH2 O CH2OH HOH2C CH2CH=CHCH3 (四四)ClaisenCondensatio

13、n 2 1. NaOC2H5 C O OC2H5H3C 2.H3O C O OC2H5CCH2 O H3C Mechanism verystrongbase (C6H5)3CNa -Handno -H C2H5ONa + H C O OC 2H5 HC CH 2C C6H5CH(COO C2H5)2 H3C C O OC 2H5 2. H3O 1. OO OC 2H5 C2H5O C O OC 2H5C6H5CH2C O OC 2H5 C2H5ONa 2. H3O 1. + DickmanCondensation C2H5ONa 2. H3O 1. CO 2C2H5 CO 2C2H5 O CO

14、 2C2H5 intramolecular C2H5ONa 2.H3O 1. CO2C2H5 CO2C2H5 + C2H5O2C C2H5O2C C2H5ONa 2.H3O 1. O O CO2C2H5C2H5O2C CO2C2H5 CO2C2H5 CO2C2H5 CO2C2H5 O O C2H5O2C C2H5O2C + intermolecular ketoneandeste C2H5ONa 2.H3O 1. C2H5CO2C2H5+ C2H5ONa 2.H3O 1. CH3CC6H5 O C6H5CCH2CC6H5 OO CO2C2H5 COCH3 O O 1.acidandbase K

15、OH + NaOH R C O NH2 NH O O + H2O NNa O O NH O O NK O O + H2O pKa 9.6 pKa7.4 P-conjugation pH=7 酰亚胺 N O O Br NBS (五)、Properties of Amide 2.HofmanDegradation + Br2 RC O NH2 CO32- OH RNH2 Mechanism 制备：伯胺和氨基酸 重排，迁移基团构型不变 Br2 CC O NH2 OH rea.-SN2 (S)-(+) C6H5 H3C H CNH2 C6H5 H3C H (S)-(-) 3.Dehydration/D

16、ehydrolysis dehydrolyzingagent:P2O5,POCl3,SOCl2 +H2O RC O ONH4 -H2O SOCl2 RCN CH3(CH2)4CN RC O NH2 +H2O -H2O H3C(H2C)4C O NH2 CONH2 Cl P2O5 CN Cl (六六)、DarzenReaction C2H5ONa +ClCH2CO2C2H5RCR(H) OOR (H)RCO2C2H5 O KOC(CH3)3 +ClCH2CO2C2H5 O CO2C2H5 Mechanism ClCHCO2C2H5 RO OR (H)RCO2C2H5 H ClCHCO2C2H5

17、O C H CR (H)R CO2C2H5 RC O R(H) Cl Using CH2CO2C2H5+ OC6H5 H3CCO2C2H5 Br NaOC2H5 C6H5C O CH3 OC6H5 H3CC O O H C6H5CCH CH3 OH C6H5 H CCH CH3 O a.OH/H2O b.H 四、四、Preparation (一一)、由羧酸制备、由羧酸制备 Chapter11 (二二)、由羧酸衍生物间互相转化制备、由羧酸衍生物间互相转化制备 NH3/ RCONH2 RCOCl (RCO)2O RCO2Na NaOH H2O H2O NH3 NH3 RCN P2O5/ NH3 R

18、CO2H a.OH/H2O b.H H/ROH HorOH/H2O RCO2R ROH P2O5 SOCl2orPCl5 RCl ROH HorOH/H2O （三酮肟重排制备（三酮肟重排制备N-取代酰胺取代酰胺 BeckmanRea. C R R N OH H CRNHR O Rea. Catalyst: H2SO4, HCl, PPA, PCl5, PhSO2Cl, CH3COCl C R R N OH H CRN C R R N OH2 -H2O R CRN R H2O C H2O R NR H C HO R NRC O R NHR Mechanism: 异构体（EZ） C C6H5 H3

19、C N OH H2NOH + ZE C O C6H5CH3 C C6H5 H3C N OH CH3 O H2NOH CH3 N OH 优先基团：芳基烷基 C C6H5 H3C N OH 75100% + PCl5 CC6H5H3CN H O CCH3C6H5N H O 构型 C C H3C N OH H2SO4 CH3 C6H5 H H NCCH3C CH3 C6H5 H O 五、五、AcetoactaticEster (一一)KetoForm-EnolFormTautomerism ketoform92.5% CH3CCH2CO2C2H5 O enolform7.5% C H C C H3C

20、 O OC2H5 O H 双重特性 ketone:HCN ,NaHS O3,NH 2OH,C6H5NHNH2 enolform:Br2/CCl4,F eCl3 tautomerism CHC O CHN O CNOH CHCN CCNH CHNO O NHCO C NOH O N C OH （二酮式分解和酸式分解（二酮式分解和酸式分解 H3CC O H2 CC O OC2H5 H3CC O CH3 H3CC O OH dil.NaOH con.NaOH Mechanism （三合成应用（三合成应用 H3CC O H2 CC O OC2H5 HC C O CH3 NaOC2H5 H3CC O C

21、HCO2C2H5 R-X a.OH/H2O b . H3O H3C C O CHCO2C2H5 R NaOC2H5 H3C C O CCO2C2H5 R H3C C O CH2 R R-X H3C C O CCO2C2H5 R R a.OH/H2O b . H3O H3C C O CH R R + + CH3CCH2CO2C2H5 O a.C2H5ONa b.n-C4H9Br CH3CCHCO2C2H5 O C4H9-n a.NaOH/H2O b.H3O CH3CCH2 O C4H9-n 制备二酮制备二酮 CH3CCH2CO2C2H5 O CH3CCHCO2C2H5 O ClCH2Cl CH3

22、CCH O CO2C2H5 H2 CCHCCH3 CO2C2H5 O CH3CCH2 O CH2CCH3 O CH2 C2H5ONa a.OH/H2O b.H3O 2 环酮 CH2CH2CO2C2H5 CH2CH2CO2C2H5 CO2C2H5 O CO2C2H5 O C2H5 O C2H5 a.C2H5ONa a.OH/H2O b.H3O a.C2H5ONa b.C2H5Br b.H3O/ -烃化烃化或或酰化酰化 dil.OH con.OH RX CH3CCH O R CO2C2H5 HOCCH2 O R CH3CCH2 O R dil.OH con.OH CH3CCH O C CO2C2H

23、5 CH3CCH2 O C O R O R HOCCH2 O C O R X C O R 六、丙二酸二乙酯合成应用六、丙二酸二乙酯合成应用 H5C2OCCH 2 O C O OC2H5 H2C CO 2C2H5 CO 2C2H5 NaOC 2H5 HC CO 2C2H5 CO 2C2H5 RX CH CO 2C2H5 CO 2C2H5 R a.OH /H 2O b.H3O/ CH 2 CO 2H R NaOC 2H5 C CO 2C2H5 CO 2C2H5 R RX C CO 2C2H5 CO 2C2H5 R R a.OH /H 2O b.H3O/ H CCO2HR R 羧酸制备方法羧酸制备方

24、法 1.取代乙酸取代乙酸 H2C CO2C2H5 CO2C2H5 a.NaOC2H5 a.OH/H2O b.H3O/ b.CH3(CH2)2Br CH2COOHCH3(CH2)2 CH3(CH2)2CH(CO2C2H5)2 2.二元羧酸 H2C CO2C2H5 CO2C2H5 NaOC2H5 a.OH/H2O b.H3O/ BrCH2CH2Br HC CO2C2H5 CO2C2H5 CH(CO2C2H5)2 (CH2)2 CH(CO2C2H5)2 CH2COOH (CH2)2 CH2COOH 22 H2C CO2C2H5 CO2C2H5 a.NaOC2H5 a.OH/H2O b.H3O/b.H

25、5C2O2CCHBr CH3 CH(CO2C2H5)2 CHCO2C2H5 H3C CH2COOH CHCOOHH3C 3环烷酸 H2C CO2C2H5 CO2C2H5 a.NaOC2H5 a.OH/H2O b.H3O/ b.Br(CH2)3Br CO2C2H5 CO2C2H5 COOH 七、碳酸衍生物 C O OH urea phosgene thioureaguanidine HOC O LHOC O LL C O ClClC O NH2H2N C NH NH2H2N C S NH2H2N hydrolysis,alcohlysis,aminolysis C O Cl ROH H2O -HCl 2NH