14β—二羰基化合物

（重點△，難點★）

14.1★β—二羰基化合物的酸性與烯醇負離子的穩定性14.2β—二羰基化合物碳負離子的反應14.3△丙二酸酯在有機合成上的應用14.4△克萊森(酯)縮合反應—乙酰乙酸乙酯的合成14.5△乙酰乙酸乙酯在有機合成上的應用14.6碳負離子和α,β—不飽和羰基化合物的共軛加成—麥克爾反應β-二羰基化合物:

指兩個羰基被一個碳原子隔開的一類化合物。Compoundshavingtwocarbonylgroupsseparatedbyaninterveningcarbonarecalledβ-dicarbonylcompounds,andthesecompoundsarehighlyversatilereagentsfororganicsynthesis.βαtheβ-dicarbonylsystemCentraltothechemistryofβ-dicarbonylcompoundsistheacidityofprotonslocatedonthecarbonbetweentwocarbonylgroups.ThepKa

forsuchaprotonisintherange9-11.pKa=9-11§14.1酮-烯醇互變結構炔烴Kucherov反應中：酮式烯醇式見第三章3.5.2（5）

酮式烯醇式

沸點：41℃(267Pa)33℃(267Pa)

分子內氫鍵p-π共軛

使烯醇式穩定共振雜化體互變異構共振雜化體與互變異構本質區別！（一）酮烯醇互變異構§14.1.1酸和堿對酮-烯醇平衡的影響酸催化：堿催化：§14.1.2化合物的結構對酮-烯醇平衡的影響單羰基化合物在平衡狀態下，烯醇式異構體的含量很少。具有β-二羰基結構的化合物在平衡狀態下，烯醇式的含量較高。原因一：分子內氫鍵；原因二：C=C鍵和C=O鍵共軛某些化合物中烯醇式含量

酮式烯醇式烯醇式含量/%有機化學OrganicChemistry活潑亞甲基具有酸性pKa=9~14pKa≈9pKa≈11pKa≈14有機化學OrganicChemistry能與羥胺和苯肼生成肟和苯腙還原得到羥基酸酯水解得到丁酮酸能與Na作用放出氫氣能使Br2/CCl4溶液退色能使FeCl3水溶液顯紫紅色與PCl5作用得到3-氯-2-丁烯酸 乙酯§14.1.3烯醇化導致立體異構化(R)-(+)-仲丁基苯基甲酮()-仲丁基苯基甲酮(R)-(+)-仲丁基苯基甲酮()-仲丁基苯基甲酮有機化學OrganicChemistry§14.2.1乙酰乙酸乙酯的合成§14.2乙酰乙酸乙酯的合成及其應用一．克萊森(Claisen)酯縮合：酯中的α-氫比較活潑，在醇鈉作用下，能與另一分子酯脫去一分子醇，生成β-酮酸酯：有機化學OrganicChemistry機理有機化學OrganicChemistry二、交叉酯縮合：兩種酯均有α-H

，四產物，無價值。只有一種酯有α-H

，兩種產物，易分離。三、Dieckmann縮合：分子內酯縮合。AMechanismForTheDieckmannCondensation+++:-:有機化學OrganicChemistry四、二乙烯酮與乙醇加成：

乙酰乙酸乙酯無色液體，有水果香味，沸點181oC，微溶于水，易溶于有機溶劑，溶于NaOH溶液，對石蕊呈中性。它不發生碘仿反應。Predicttheproductfromthebase–catalyzedcondensationoftwomoleculesofethylacetate:First,formtheenolate.First,formtheenolate.Previously,weestablishedthatthecarbonacidityofcarbonylcompoundsisimportantinsynthesisbecausethecollapseoftheenolateaniongenerateselectrondensityonthe-carbon,whichcanthenbeusedasanucleophile.

αα-carbanionTheenolateattacksasecondmoleoftheesterThisyieldsatetrahedralintermediate.Expulsionofethoxidegivesfinalproduct.Thefinalproductisaethylacetoacetate.ThisreactioniscalledtheClaisenCondensation.Predictthemajorproductforthereactionshownabove.ThisisgoingtobeaClaisen-typeCondensation(anintromolecularClaisen,orADieckmanCondensation.Theenolateofoneendattackstheotherestercarbonyltogiveatetrahedralintermediate……Whichbreaksdownwithexpulsionofmethoxide.…whichbreaksdownwithexpulsionofmethoxide.Predicttheproductfromthebase-catalyzedcondensationofethylacetateandethyl

benzoate:Theenolateattacksethyl

benzoate…

…toyieldatetrahedralIntermediate.Expulsionofethoxidegivesthefinalproduct.ThisreactionisamixedClaisen

Condensation.§14.2.2乙酰乙酸乙酯的性質一、酮式分解：稀堿作用下二、酸式分解：濃堿作用下酸式分解的機理：三、烷基取代活潑亞甲基中的氫原子乙酰乙酸乙酯與伯鹵代烷的親核取代反應：鹵代乙烯及芳基鹵化物也不發生反應有機化學OrganicChemistry一、制備甲基酮或烷基取代乙酸：§14.2.3乙酰乙酸乙酯在合成上的應用有機化學OrganicChemistry二、制備二元酮或甲基環烷基酮：2,6-庚二酮制備環烷基酮：1-苯基-1,3-丁二酮2,5-己二酮有機化學OrganicChemistry三、制備高級酮酸或β-二酮：(firstalkylation)Ethyldibutylacetoacetate(77%)Ethylbutylacetoacetate(69-72%)(decarboxylation)(hydrolysis)(secondalkylation)3-Butyl-2-heptanone4-Oxopentanoicacid+++Glutaricacid(80%fromtetraester)-:丙二酸加熱脫羧生成一元酸P439(-)::+CyclobutanecarboxylicacidHydrolysisanddecarboxylation有機化學OrganicChemistry§14.3丙二酸酯的合成及其應用一、丙二酸二乙酯的合成丙二酸二乙酯：無色液體，有水果香味，沸點199oC，微溶于水，易溶于有機溶劑。有弱酸性，pKa=13。有機化學OrganicChemistry二、制備取代乙酸：三、制備二元酸：四、制備環烷酸：§14.4Knoevenagel（諾文葛耳）縮合醛、酮在弱堿（胺、吡啶）作用下，與具有α活潑氫原子的縮合，有較高的收率。Theknoevenagelreactionisanaldol-likereactioninwhichketonesandaldehydesreactwithdiethylmalonate(丙二酸二乙酯)togiveanα-β-unsaturateddiesterEtO-/EtOHEtO-/EtOHEtO-/EtOHacidichydrogenEtO-/EtOHEtO-EtO-/EtOHEtO-Predicttheproductofthereactionshownabove:ThefirststepisasimpleClaisenCondensationbetweentheenolateandanothermoleofester.Thisgivesatetrahedralintermediatewhichbreaksdowntogivetheketo-ester.Inthesecondstep,theesterishydrolyzedtotogivea-ketoester,whichundergoesdecarboxylation.βAsymmetricketone,thehalloamrkofaClaisenCondensationlossofCO2Suggestasynthesisofethyl2,4-dicyclopentyl-3-oxobutanoateusingaClaisenCondensation:Themoleculewasformedbyexpulsionofethoxidefromatetrahedralintermediateatthiscarbon.Splitthetetrahedraladductintotwomoleculesofester…

…anddrawtheesterandthecorrespondingenolate.Completingthesynthesis:Thefirststepissimplyenolizationofenthylacetoacetatewithethoxideandcondensationwithbenzaldehyde.Usingaethylacetoacetateandbenzaldehyde,asstartingmaterials,performthesyntheticconversionasshownabove.Theadductwillundergohydrolysisanddecarboxylationintheusualmanner.The-hydroxyketonenowdehydratestogivethedesiredproduct.βNowpredicttheproductoftakingthismolecule,reactingitwithbromomethaneinthepresenceofmethoxide,followedbywork-upwithaqueousacid.Thehydrogenwhichisflankedbythetwocarbonylsisacidic,andwillformanenolateanionwhichcanattackthealkylhalide.The-ketoesterwillthenbehydrolyzedbytheacidtogivethe-ketoacid…ββ…Whichwilldecarboxylatetogivethefinalproduct…§14.5Michael加成具有活潑氫的化合物與α、β-不飽和化合物進行加成Michael加成與Claisen縮合或羥醛縮合聯用，合成環狀化合物。P477教材有誤！§14.6其他含活潑亞甲基ConjugateAdditionReactions

TheMichaelReactionRecallthemechanismfor1,4-additionreactionofdienes.allyliccarbocation1,4-additionProtonationontheterminalcarbongeneratestheallyliccarbocationwithcationiccharacteronbothcarbon#1and3Recallthemechanismfor1,4-additionreactionofdienes.Conjugatedketonesandaldehydescanundergoananalogousreactioninwhichanucleophileaddstotheterminalcarbon（末端碳原子）ofthedoublebond.NucNucNucResonanceplacescationiccharacteronbothcarbons#1and3.Aminesaddtoconjugatedketonesandaldehydestogivetheconjugateadditionproduct,almostexclusively.Knowingthis,predicttheproductofthefollowingreactions.CH3-NH2CH3-NH2CH3-NH2CH3HCN,orpreferably(CH3CH2)2AlCN,willalsoaddtoconjugateketonesandaldehydestoexclusivelygivetheconjugateadditionproduct,knowingthis,predicttheproductofthefollowingreactions.1.(CH3CH2)2Al-CN2.H3O+1.(CH3CH2)2Al-CN2.H3O+NC1.(CH3CH2)2Al-CN2.H3O+1.(CH3CH2)2Al-CN2.H3O+NC1.(CH3CH2)2Al-CN2.H3O+1.(CH3CH2)2Al-CN2.H3O+CNAlkylgroupscanbeaddedtoconjugatedketonesusingdialkylcopperlithiumreagents,Knowingthis,predicttheproductofthefollowingreactions.1.(CH3)2CuLi2.H3O+1.(CH2=CH)2CuLi2.H3O+1.(CH3)2CuLi2.H3O+1.(CH2=CH)2CuLi2.H3O+1.(CH3)2CuLi2.H3O+1.(CH2=CH)2CuLi2.H3O+Beginningwith2-cyclohexenone,suggestasynthesisofthemoleculeshownontheright.CH3fromWittigfromconjugateadditionBecausewearestartingwithanα-β-unsaturatedketone,wecanaddthephenylgrouptotheconjugateadditionwithdialkylcopperlithium;thediemethylalkenecouldbeformedfromketone,usingaWittigreaction.CH3CP+(C6H5)3CH3CP+(C6H5)3CH31.(Ph)2CuLi2.H3O+Summarizingourconjugateadditionreactions(CH3)2CuLi(CH3CH2)2AlCNCH3CNSummarizingourconjugateadditionreactions(CH3)2CuLi(CH3CH2)2AlCNCH3CNCNAdditionofHCNSummarizingourconjugateadditionreactions(CH3)2CuLi(CH3CH2)2AlCNCH3CNCNCH3AdditionofalkylgroupsSummarizingourconjugateadditionreactions(CH3)2CuLi(CH3CH2)2AlCNCH3CNCNCH3AdditionofaminesSummarizingourconjugateadditionreactions(CH3)2CuLi(CH3CH2)2AlCNCH3CNCNCH3Predicttheproductfromtheadditionofanenolateanion.(CH3)2CuLi(CH3CH2)2AlCNCH3CNCNCH3SummarizingourconjugateadditionreactionsThemechanism:newbondPredicttheproductsofthefollowingreactions:CH3OOCH3NCCNOCH3CH3CH3CH3OOCH3NCCNOCH3CH3CH3OCH3OCH3