12清华大学有机化学李艳梅老师课件chapter_12_1_Nucleophilic_additio

Aldehyde&Ketone第十二章醛和酮OrganicChemistryA(1)ByProf.LiYan-MeiTsinghuaUniversityContent12.1Introduction12.2SpectrumData&PhysicalProperties12.3NucleophilicAddition12.4Reactionsatthe-CarbonofAldehyde&Ketone12.5OtherChemicalReactions12.6Preparation12.1.1Molecularstructure12.1.2Classification12.1.3Nomenclature(Learnonyourown)12.1.4Isomerization(Learnonyourown)12.1Introduction12.1.1Molecularstructure分子结构OHROR'RAldehydeKetonePlanarmolecule12.1.2Classification分类按烃基类型：脂肪族、芳香族按羰基数目：一元、二元、三元按烃基饱和程度：饱和、不饱和其它：单酮/混酮，环（内）酮OR'RR=R’单酮RR’混酮H2CC(CH2)12CHH3CO环（内）酮12.1.3Nomenclature(Learnonyourown)12.1.4Isomerization(Learnonyourown)12.2.1IRspectrum12.2.2NMRspectrum12.2.3Physicalproperties12.2.4Isomerization(Learnonyourown)12.2SpectrumData&PhysicalPropertiesC=ORCHO1720-1740cm-1ArCHO1695-1715cm-1RCOR1700-1725cm-1ArCOR1680-1700cm-1ArCOAr1660-1670cm-1共轭后降低约30cm-1CO－H2665-2880cm-112.2.1IRspectrum1HNMR:CHO9-10ppm-CO-CH2-2.0-2.5ppm-CO-CH32.0-2.5ppm13CNMR:-CHO175-205ppmR-CO-R’200-220ppm12.2.2NMRspectrum分子极性大，与水可形成氢键。香型：低级醛：强烈的刺激味中级醛：果香味玫瑰香香油香味主要成分樟脑香味麝香香味12.2.3PhysicalpropertiesH3CCH2OH2CC(CH2)12CHH3COC6H5CH2CH2COCH3CH3(CH2)7CHO带部分正电被亲核试剂进攻加成既可被氧化，也可被还原一定的酸性CHCO12.3.1Generalreaction,ReactivityandStereochemistry12.3.2Reactionwithoxygennucleophiles12.3.3ReactionwithSulfurnucleophiles12.3.4ReactionwithCarbonnucleophiles12.3.5Reactionwithnitrogennucleophiles12.3NucleophilicAdditionGeneralReaction:(A).Reaction12.3.1Generalreaction,ReactivityandStereochemistryCRRO(H)+E-NuCRNuROE(H)碱性条件：酸性条件：1、电子效应：超共轭效应，羰基化合物的稳定性2、空间效应：(B).ReactivityCRRO(H)+H-NuCRNuROH(H)sp2sp31200109.50(C)Stereochemistry羰基平面两侧等价CramruleHCH3O-NuHCH3NuO-羰基平面两侧不等价主要产物12.3.2Reactionwithoxygennucleophiles与含氧亲核试剂的加成(A)Hydration偕二醇(B)Additionofalcohols半缩醛缩醛半缩酮缩酮注：1、为醚类化合物2、简单的醛与过量的醇：反应容易简单的酮与过量的醇：反应不容易3、缩醛（酮）碱性条件下稳定，在酸性水溶液中水解：用途：保护羰基保护羟基COOHHOCOOH3+OCO10.3.3ReactionwithSulfurNucleophiles与含硫亲核试剂的加成(A)加NaHSO3条件：1、醛、脂肪族甲基酮及C8以下环酮2、“过量”、“饱和”的NaHSO3应用：1、鉴别：产物为白色沉淀2、分离、纯化：(B)AdditionofRSH缩硫酮缩硫酮特点：1、直接生成缩硫醛（酮）2、缩硫醛（酮）很难分解为原酮（醛）：无法用于保护羰基应用：还原羰基COSHSHCSSH3OCOH2,NaneyNiCHH+NiS+CH3CH3(C)与Schiff试剂的反应品红＋SO2(g)品红醛试剂（Schiff试剂）酮甲醛＋Schiff试剂紫红不褪色其它醛紫红褪色＋H2SO4用途：鉴别10.3.4ReactionwithCarbonNucleophiles与含碳亲核试剂的加成(A)与HCN条件：醛、脂肪族甲基酮及C8以下环酮酸碱性的影响（略偏碱）(B)与炔化物反应COHHRMgXCOMgXHHRH2OCOHHHR10ROH(C)与金属有机化合物反应COHR'RMgXCOMgXHR'RH2OCOHHR'R20ROHCOR''R'RMgXCOMgXR''R'RH2OCOHR''R'R30ROH(D)与磷ylide的反应－－Wittig反应制备：带有相邻“＋”“－”电荷的分子（内鎓盐）(Ph)3PCR1R2OC(Ph)3PCR1R2CO(Ph)3PCR1R2COP(Ph)3OCCR1R2+10.3.5ReactionwithNitrogennucleophiles与含氮亲核试剂的加成(A)与胺反应：10胺CO+RH2NCO-N+H2RCNRHOH质子交换－H2OCNR亚胺注意：1、亚胺不稳定，尤其是脂肪族亚胺；芳胺相对较稳定，可分离出。2、书写法：脱水3、用途：亚胺用于保护羰基与胺反应：20胺与胺反应：30胺不反应烯胺可水解当该羰基化合物含有-H时(B)与氨及其衍生物反应：1、与氨的反应脂肪族亚胺不稳定CO+NH3CNH2OHCNH2、与氨的衍生物的反应可稳定存在CO+H2N-YCNH-YOHCN-Y反应特点：1、产物多为白色固体：用于鉴别醛酮2、产物一般有固定的结晶形状及熔点：可通过测熔点来推测未知的醛酮3、产物在稀酸作用下水解为原反应物：可用于分离、提纯反应类型总结：1、简单加成：Nu-中带负电荷的部分加在羰基碳原子上，另一部分加在氧原子上。2、先加成后取代－－酸催化下如：与ROH，RSH3、先加成后消去－－酸或碱催化如：胺、氨及氨的衍生物CRR'ONCHR''MgXHOHNaO3SH注意：以上反应除与有机金属化合物的反应之外，均为平衡过程讨论参数：平衡常数12.4.1Acidityofthe-hydrogens12.4.2Keto-EnolTautomerization12.4.3Application12.4Reactionsatthe-CarbonofAldehyde&KetoneNucleophilicAdditiontotheCarbonylGroupOxygenNucleophilesSulfurNucleophilesCarbonNucleophilesNitrogenNucleophilesReactionsatthe-CarbonofCarbonylCompoundsAcidityofthe-hydrogensKeto-EnoltautomerizationApplications12.4.1Acidityofthe-hydrogens-H的酸性OCCRCCCHHOHydrogensareunusuallyacidic(pKa=19-20)Hydrogensarenotacidic(pKa=40-50)pKaC2H650C2H444NH334C2H225CH3COCH320C2H5OH15.9H2O15.74Ph-OH10H2CO36.5KetoEnol12.4.2Keto-EnolTautomerization醛（酮）－烯醇式互变异构A.Interconversion转化过程B.Keto-enoltautomersinequilibrium平衡K＝[enol][keto]平衡常数：K＝[烯醇][醛或酮]Monocarbonylcompounds单羰基化合物(99%)(1.5×10-4%)(100%)(extremelysmall)(98.8%)(1.2%)COH3CHCOHH2CHCOH3CCH3COHH2CCH3OOH以醛（酮）式为主-dicarbonylcompounds-二羰基化合物24%76%H3CCCH2CCH3OOH3CCCHCCH3OHOOCCCOHCH3H3CHOCCCOHCH3H3CH烯醇式含量增大Phenol酚K1014OOH烯醇式含量几乎为100％C.Detection检测PurpleorblueH3CCCHCCH3OHOH3CCCHCCH3OO6FeFeCl3D.Formationofenolate烯醇盐的形成Which“Base”?用什么碱来形成烯醇盐？HCCHOCCOCCOBO+LiNOLi+HN+NHdiisopropylaminepKa=35LibutyllithiumTHF-78oC+NLilithiumdiisopropylamideLDAbutanepKa~50HCCHOLDACCOCCO(CH3)3SiClCCOSi(CH3)3enolateCOH3CH3CK+H-COKH2CH3CH2E.RegioselectiveFormationofEnolateAnions形成烯醇盐的区域选择性??KineticenolateThermodynamicenolateGenerally:1.Lowtemperaturegivesthekineticenolate.2.Hightemperature,relativelyweakbaseinaproticsolventgivesthethermodynamicenolate.LDATwospecialexamples:两个特殊情况1.Thekineticallyfavoredenolatecanbeformedcleanlythroughtheuseofdiisopropylamide(LDA).采用LDA作为碱时易生成动力学控制的烯醇盐2.Inacidcondition,thethermodynamicenolisformedpredominantly.酸性条件下易生成热力学控制的烯醇thermodynamicenolkineticallyfavoredenolateF.Racemization异构化CCHCH3C2H5CCCH3C2H5BaseOOabbCCCH3C2H5OH(R-)(S-)aNucleophiliccenterC-亲核中心（试剂）NucleophiliccenterO-亲核中心（试剂）Ambidentnucleophile“两可亲核试剂”“两可离子”Carbanion碳负离子alkoxideanions烷氧基负离子HCCHOCCOCCOB12.4.3Application应用KetoEnolWhichmakesagreatercontributiontothehybrid?两个极限式，哪个贡献大？A.Reactasanalkoxideanions作为烷氧基负离子trappedOHNaOHORIORCOH3CCH2-COH3CCH2(CH3)3Si-ClTHFCOSi(CH3)3H3CCH2烯醇式含量很高的结构易发生O-烷基化反应，如：酚或采用氯硅烷来捕获React