有机化学Chap11CarboxylicAcidsandSubstitutedCarboxylicAcids

Chapter11CarboxylicAcidsandSubstitutedCarboxylicAcids,IntroductiontoCarboxylicAcids,AceticacidButanoicacidHexanoicacidLacticacid乙酸丁酸己酸乳酸,Acetylsalicylicacid阿司匹林,4-Aminosalicylicacid4-氨基水杨酸,Isotretinoin异维A酸,Section1CarboxylicAcids,Carboxylgroup,1Structure,ClassificationandNomenclature,1.1Structure,1Structure,ClassificationandNomenclature,sp2hybrids,p-conjugation,Electrostaticpotentialmap(静电势能平面图),1.2Classification,1Structure,ClassificationandNomenclature,Aliphaticacid,Aromaticacid,Monobasicacid,Polybasicacid,butanedioicacid丁二酸(succinicacid,琥珀酸),propionicacid丙酸,Inthesystematicnomenclature,thefinal“e”oftheparentalkaneisdroppedandthesuffix“oicacid”isadded.Diacidsarenamedsimilarly,exceptthatthesuffixis“dioicacid”,andthefinal“e”isnotdropped.Cyclicacidsarenamedas“cycloalkanecarboxylicacids”.,1.3Nomenclature,1Structure,ClassificationandNomenclature,选择含羧基的最长碳链作为主链；编号：靠近羧基一端编号，编号尽可能小；取代基位次之和最小；,1.3Nomenclature,1Structure,ClassificationandNomenclature,中文命名法：,3-bromobutanoicacid3-溴-丁酸,3-ethylbenzoicacid3-乙基-苯甲酸,4-aminocyclohexanecarboxylicacid4-氨基环己甲酸,benzoicacid苯甲酸,1Structure,ClassificationandNomenclature,4321,ethanedioicacid乙二酸(oxalicacid,草酸),(E,E)-2,4-hexadienoicacid(E,E)-2,4-己二烯酸acidsorbicacid,山梨酸,1Structure,ClassificationandNomenclature,甲酸(蚁酸),乙酸(醋酸),1.,2.,2PreparingCarboxylicAcids,4.,2PreparingCarboxylicAcids,无水乙醚,3.PhysicalProperties,Aceticaciddimer,2-Methyl-1-butene,2-Butanone,2-Butanol,Propanoicacid,沸点,318099141,4.ChemicalProperties,p-conjugation,酸性(Acidity),羧酸衍生物的形成(Derivativesofcarboxylicacids),还原反应(Reduction),-H的卤代(Halogenationof-hydrogens),二元酸的热解反应(SpecialReactionofDibasicacids),脱羧反应(Decarboxylation),isasymbolwhichcombineAandRtogether,itmeansarylgroupsoraliphaticgroups.,Sequenceofacidity:,4.1Acidity,4.ChemicalProperties,4.1.1Acidity,4.1Acidity,4.ChemicalProperties,4.1.1Acidity,Acetateion羧酸离子,PenicillinGisanorganicmolecule,whycanitdissolveinwaterofinjection?,Wecanutilizethecarboxylgrouptoproducesodiumsaltorpotassiumsalt.Thesesaltscanbedissolvedinwatereasily.,BenzylpenicillinSodium(potassium)青霉素钠(钾),4.ChemicalProperties,Ethanol醇,Ethoxideion醇盐离子(localizedcharge局域电荷),Aceticacid羧酸,Acetateion羧酸离子(delocalizedcharge离域电荷),4.1.2.1Acidsbearingelectron-donatinggroupsareweakeracidsthantheirparentcompounds.,HCOOHCH3COOHCH3CH2COOHpKa3.774.764.86,4.ChemicalProperties,4.1.2SUBSTITUENTSANDACIDSTRENGTH(取代羧酸的酸性),4.1.2.2Acidsbearingelectron-withdrawinggroupsarestrongeracidsthantheirparentcompounds.Thestrongerelectron-withdrawingeffect,themoreacidityoftheacid;Thefurthertheelectron-withdrawinggroupfromtheacid,thesmallertheeffect.,4.ChemicalProperties,FCH2COOHClCH2COOHBrCH2COOHCH3COOHpKa2.672.872.904.76,4.1.2.3Carboxylhasstrongerelectron-withdrawingeffect,sothedicarboxylacidhavestrongeraciditythancarboxylacid.Asthechainlengthbetweentwocarboxylsincrease,theaciditysteadilydecreases.,HOOCCOOHHOOCCH2COOHHOOC(CH2)2COOHCH3COOHpKa1.462.804.174.76,4.ChemicalProperties,pKa4.17,-conjugation,Thoughthebenzeneringiselectron-withdrawinggroup,benzoicacidhasweakeraciditythanmethanoicacidbecauseoftheconjugatedsystemformedbetweenthebigbondandthecarboxyl(-conjugation).Butbenzoicacidhasstrongeraciditythanotheraliphaticmonobasicacids.,HCOOHCH3COOHCH3CH2COOHpKa3.774.764.86,4.ChemicalProperties,FCH2COOHClCH2COOHBrCH2COOHICH2COOHHOCH2COOHCH3COOH2)FCH2COOHFCH2CH2COOHFCH2CH2CH2COOH3)CF3COOHF2CHCOOHFCH2COOH,Thesequenceofacidity:,4.ChemicalProperties,carboxylicacid,acidchloride,ester,amide,anhydrides,4.ChemicalProperties,4.2Formationofderivativesofcarboxylicacids,4.ChemicalProperties,4.2Formationofderivativesofcarboxylicacids,Methylbutanoate甲酸丁酯(pineapple),Isopentylacetate异戊酸乙酯(banana),Butylacetate丁基乙酸酯(pear),Thestructureofprotein,4.2Formationofderivativesofcarboxylicacids,4.2.1Ester(酯化反应Esterification),4.ChemicalProperties,TheFischerEsterificationProcess,sp2,sp3,sp2,EstersAsProdrugs,Glaucoma青光眼,Drugscontaininghydroxylgroupsareoftenconvertedintoprodrugstoachievebetterabsorptionproperties.,Epinephrinehydrochloride盐酸肾上腺素,Dipivefrinhydrochloride盐酸地匹福林,EstersAsProdrugs,Chloramphenicol氯霉素,Chloramphenicolpalmitate棕榈酸氯霉素,EstersAsProdrugs,4.2.2Acylhalide,4.ChemicalProperties,氯化亚砜,亚磷酸,三氯氧酸,4.2.3Anhydrides,4.ChemicalProperties,phosphoruspentoxideDehydrant,4.2.4Amide,4.ChemicalProperties,Sedatives,Melatonin(褪黑激素)美拉酮宁/松果腺素insomnia失眠,Zolpidem(唑吡坦)AmbienTM,Zaleplon(扎来普隆)SonataTM,(思诺思/乐坦/诺宾),(思威坦/安蓝/安云),Anxiolyticagents,Benzodiazepines(苯二氮卓类),Sedatives,Oxazepam(奥沙西泮)Prazepam(普拉西泮)(SeraxTM)去甲羟安定(VerstranTM)环丙安定,Diazepam(地西泮)(ValiumTM)安定,“团结就是力量”,“锁链化学”,PolyamidesandPolyesters,CelluloidNitrate赛璐珞,Bakelitebuttons,Bakelite酚醛树脂(1907),PolyamidesandPolyesters,WallaceCarothers华莱士卡罗瑟斯(1896年1937年),PolyamidesandPolyesters,杜邦公司,对苯二甲酸Adiacid,乙二醇Adiol,聚对苯二甲酸乙二醇酯Polyethyleneterephthalate(PET),PolyamidesandPolyesters,Dacron(涤纶)(apolyester)“的确良(凉)”,六亚甲基二胺Adiamine,PolyamidesandPolyesters,己二酸Adioicacid,Nylon-6,6(尼龙)(apolyamide),KevlarTM(芳纶),PolyamidesandPolyesters,4.3Reduction,Lithiumaluminiumhydride(LiAlH4)canreducecarboxylgroupbutcannotreducecarbon-carbondoublebond,thatmakeitaselectivereductant.Thereductiveabilityofsodiumborohydride(NaBH4)isnotstrongenoughtoreducecarboxylicacids.,4.ChemicalProperties,4.4Halogenationof-hydrogens(-氢的卤代),4.ChemicalProperties,4.5Decarboxylation(脱羧反应),hightemperature,4.ChemicalProperties,4.6SpecialReactionofDibasicacids,Ethanedioicacid(乙二酸)(Oxalicacid草酸),4.ChemicalProperties,Propanedioicacid(Malonicacid丙二酸),Butanedioicacid(Succinicacid,琥珀酸),4.ChemicalProperties,Pentanedioicacid(Glutaricacid,谷酸),Butanedioicanhydride丁二酸酐(琥珀酸酐),pentanedioicanhydride戊二酸酐,Phthalicanhydride邻苯二甲酸酐,4.ChemicalProperties,Hexanedioicacid己二酸(adipicacid),4.ChemicalProperties,Heptanedioicacid庚二酸(pimelicacid),(n6),hightemperture,4.ChemicalProperties,n,nHOOC(CH2)nCOOH,CarboxylicAcid羧酸,Summary,酸性,HOOCCOOHFCH2COOHClCH2COOHBrCH2COOHICH2COOHHOCH2COOHHCOOHC6H5COOHCH3COOH2)FCH2COOHFCH2CH2COOHFCH2CH2CH2COOH,CarboxylicAcid羧酸,Summary,1,2,3,4,酸性,羧酸衍生物的形成,还原反应,-H的卤代,脱羧反应,5,Summary,Dibasicacid,二元酸的热解反应,6,Analysis:,Exercise:,Section2SubstitutedCarboxylicAcids,Classification,Halogenoacid卤代羧酸,Aminoacid氨基酸,Hydroxyacid羟基酸,Alcoholicacid醇酸,Phenolicacids酚酸,Ketoacid酮酸,Aldehydoacid醛酸,Carbonylacid羰基酸,1HydroxyAcids,1.1.1AlcoholicAcid,1.1ClassificationandNomenclature,-Alcoholicacids-羟基酸,Lacticacid乳酸2-羟基丙酸,Citricacid柠檬酸2-羟基丙烷-1,2,3-三羧酸,1.1.2PhenolicAcids,1HydroxyAcids,2-羟基苯甲酸水杨酸,3,4,5-三羟基苯甲酸五倍子酸,没食子酸,3,4-二羟基苯甲酸原儿茶酸,1.2Preparationofalcoholicacid,Halogenatedacid卤代酸,Cyanhydrin氰醇,1HydroxyAcids,1.3PhysicalProperties,1.4ChemicalProperties,The-Ieffectdecidethesequenceoftheacidity.,1.4.1Acidity(酸性),1HydroxyAcids,Alcoholicacid,卤代羧酸,醇酸,pka3.004.124.174.54,1HydroxyAcids,Phenolicacids,羟基的双重效应：共轭和诱导效应，作用相反；诱导效应：酚羟基氧电负性高，使苯环电子云向氧移动，则羧基基中羟基H更易于解离；即吸电子诱导效应(I效应)；共轭效应：p-共轭；电子由高密度集中苯环转向苯环与羟基间；即给电子共轭效应(+C效应)；,p-phenolicacids,m-phenolicacids,o-phenolicacids,Inductiveeffect,p-conjugation,1HydroxyAcids,Phenolicacids,+C,I,I,吸电子基团：NO2CNFClBrICCHOCH3C6H5CHCH2H供电子基团：(CH3)3C(CH3)2CHCH3CH2CH3H,诱导效应：,以氢H为比较标准，如果电子云偏向取代基，则该取代基具有吸电子的诱导效应(I效应)；如果如果电子云偏离取代基，则该取代基具有供电子的诱导效应(+I效应)；,1HydroxyAcids,Phenolicacids,吸电性共轭效应(C效应)：等吸电子基团取代时，能降低共轭体系的电子密度，产生吸电性共轭效应，其电子云转移方向与基团吸电性的I效应一致；供电性共轭效应(+C效应)：等基团取代时，由于p共轭增加了共轭体系的电子云密度，产生供电性共轭效应，其电子云转移方向与基团吸电性的I效应相反；,共轭效应：,1HydroxyAcids,Phenolicacids,Exercise:Explainthesequenceofacidityofthefollowingacids?,I,位阻,氢键,I,+C,-C,I,位阻,氢键,I,Lactide丙交酯,1.4.2Dehydration,-Alcoholicacids,1HydroxyAcids,1HydroxyAcids,3-溴-2-羟基丁酸,六元环交酯,-unsaturatedcarboxylicacid,-不饱和羧酸,-Alcoholicacids,1HydroxyAcids,-butyrolactone-丁内酯,Sodium-hydroxybutyrate-羟基丁酸钠,-alcoholicacids,intravenousanaesthetics静脉麻醉药,1HydroxyAcids