郑州大学有机化学8卤代烃金属有机化合物.ppt

Chapter 8 Halohydrocarbons(卤代烃卤代烃)Organometallic Compounds(有机金属有机金属化合物化合物)8.1 Classification(分类分类),Nomenclature(命名命名),Structure(结构结构)and Physical Properties(物理性质物理性质)Saturated halohydrocarbons(饱和卤代烃饱和卤代烃)Unsaturated halohydrocarbons(不饱和卤代烃不饱和卤代烃)Aromatic halohydrocarbons(芳香卤代烃芳香卤代烃)按卤素所连接的烃基的结构分类按卤素所连接的烃基的结构分类Benzylic halides(苄型卤代烃苄型卤代烃,苄基卤苄基卤)Aryl halides(芳型卤代烃芳型卤代烃,芳基卤芳基卤)Allylic halides(烯丙型卤代烃烯丙型卤代烃,烯丙基卤烯丙基卤)Vinylic halides(乙烯型卤代烃乙烯型卤代烃,乙烯基卤乙烯基卤)Propgarpyl halides(炔丙型炔丙型卤卤代代烃烃)按与卤素相连的碳原子的级数分类按与卤素相连的碳原子的级数分类伯伯(1)卤代烃卤代烃仲仲(2)卤代烃卤代烃叔叔(3)卤代烃卤代烃按分子中卤素的数目分类按分子中卤素的数目分类一卤代烷一卤代烷 多卤代烷（邻二卤代烷多卤代烷（邻二卤代烷 偕二卤代烷）偕二卤代烷）CH2Cl2二氯甲烷二氯甲烷8.2 ReactionsNucleophilic Substitution(亲核取代亲核取代)：SN1/SN2)Elimination Reactions(消除反应消除反应):E1/E2Reduction(还原还原)Formation of Organomatelic Compounds(形成金属有机化合物形成金属有机化合物)8.2.1 Nucleophilic Substitution(亲核取代亲核取代)8.2.1.1 SN1 and SN2SN2Kineticsbimolecular nucleophilic substitution(双分子亲核取代双分子亲核取代)v=kCH3BrOH-Mechanismsingle-step reaction(一步反应一步反应)Stereochemistrysecond order The nucleophile attacks the carbon bearing the leaving group from the BACK SIDE.Inversion of configuration(构型翻转构型翻转):Walden inversion Energy DiagramSide ReactionE2SN1Kineticsunimolecular nucleophilic substitution(单分子亲核取代单分子亲核取代)v=kt-BuClMechanismMultistep reaction(多步反应多步反应)StereochemistryRacemizationIon-pair Mechanism(离子对机理离子对机理)Close ion-pair loose ion-pair free ions(紧密离子对紧密离子对)(松散离子对松散离子对)(自由离子自由离子)Energy DiagramR3CXSide ReactionRearrangement and E18.2.1.2 Factors affecting SN1 and SN2The structures of alkyl groups(烃基的结构烃基的结构)Leaving groups(离去基团离去基团)The nucleophile(亲核试剂亲核试剂)The solvent(溶剂溶剂)8.2.1.2.1 The structures of alkyl groups0(CH3)3CX30.00001(CH3)3CCH2XNeopentyl0.02(CH3)2CHX21CH3CH2X130CH3XMethylRelative RateCompoundSubstituentSteric effectSN2SN11,200,000(CH3)3COH3(CH3)3CBr12(CH3)2CHOH2 (CH3)2CHBr1.0CH3CH2OH1 CH3CH2Br1.0CH3OHMethylCH3BrRelative rateProductTypeAlkyl halideStability of the carbocationsSN1反应速度反应速度:PhCH2X,CH2=CHCH2X 3RX 2RX 1RX CH3X CH2=CHX,PhX(CH3)3CCH2Cl为何既难以发生为何既难以发生SN2又难以发生又难以发生SN1?SN2SN2反应速度反应速度:PhCH2X,CH2=CHCH2X CH3X 1RX 2RX 3RX CH2=CHX,PhX对于对于苄基卤、烯丙基卤苄基卤、烯丙基卤，SN1和和SN2均容易发生；对于均容易发生；对于乙烯型卤、芳基卤乙烯型卤、芳基卤，SN1和和SN2均难以发生；使用非常强的碱，如均难以发生；使用非常强的碱，如NaNH2，将使其发生消除反应，分别，将使其发生消除反应，分别得到炔烃、苯炔得到炔烃、苯炔(会进一步发生加成会进一步发生加成)?8.2.1.2.2 Leaving groupsGood L(好的离去基团好的离去基团)离去基团对离去基团对SN2和和SN1具有类似的影响，但对具有类似的影响，但对SN1影响程度更大影响程度更大Weakly basic(碱性弱碱性弱)HL Strong acid(强酸强酸)Stable(稳定稳定)-I -Br -Cl -F离去能力离去能力 其它常见的离去基团其它常见的离去基团 -OTs对甲基苯磺酸酯基对甲基苯磺酸酯基-OSO2C6H4CH3-p-OMs甲基磺酸酯基甲基磺酸酯基-ONs对硝基苯磺酸酯基对硝基苯磺酸酯基-OSO2C6H4NO2-p-OSO2OR烷基硫酸酯基烷基硫酸酯基0120010,00030,00060,000Relative reactivityHO,H2N,ROFClBrITsOLeaving group离去基团的离去顺序：离去基团的离去顺序：-N+N -O+R2 -OSO2C6H4NO2-p -OSO2Ph -OSO2C6H4CH3-p -OSO2CH3 -I -O+H2 -Br -Cl 硫酸二甲酯硫酸二甲酯是个很好的是个很好的甲基化甲基化试剂，试剂，常用于和醇反应得到常用于和醇反应得到甲基醚甲基醚SN1G=OCH3 CH3 H Cl NO2速率速率 1.0 1.6 3.1 8.4 558.2.1.2.3 The nucleophile试剂的亲核性对试剂的亲核性对SN1的反应速率影响很小，对的反应速率影响很小，对SN2影响很大影响很大 1)Nucleophilicity and basicityBasicity(碱性碱性):the affinity of a base for a proton(与质子的结合能力与质子的结合能力)Nucleophilicity(亲核性亲核性):the affinity of a Lewis base for a carbon atom(与碳原与碳原子的结合能力子的结合能力)亲核性亲核性除与除与碱性碱性有关外，还与有关外，还与可极化度可极化度(Polarizability)有关有关Polarizability(可极化度可极化度):the ease with which the electron distribution around an atom is distorted by a nearby electric field(核外电子分布受外界电场影响而核外电子分布受外界电场影响而发生扭曲变形发生扭曲变形)Larger atoms are more polarizable.I Br Cl FS O质子溶剂中亲核性质子溶剂中亲核性 I-F-：1)可极化度可极化度;2)溶剂化效应溶剂化效应 a.In a group of nucleophiles in which the nucleophilic atom is the same,nucleophilicities parallel basicities(试剂中亲核原子相同时，亲核性与碱性一致试剂中亲核原子相同时，亲核性与碱性一致).RO-HO-ArO-RCOO-ROH H2Ob.Nucleophilicity decrease to the right in an row of the peridoic table(同一周期同一周期中亲核性自左向右逐渐降低，与碱性一致中亲核性自左向右逐渐降低，与碱性一致).NH2-OH-F-R3C-R2N-RO-F-c.Nucleophilicity usually increases in going down a column of the periodic table(同一主族自上而下亲核性增强，与碱性相反同一主族自上而下亲核性增强，与碱性相反)(在在质子溶剂质子溶剂中中).F-Cl-Br-I-HO-HS-RO-CN I NH3 NR3 RO-HO N3 Br ArO CH3COO Cl H2O F In aqueous ethanol17001,00016,00025,000100,000125,000125,000Relative reactivityH2ONH3ClHOCH3OICNHSNuSN2Polar aprotic solvents(偶极溶剂偶极溶剂,极性非质子溶剂极性非质子溶剂)DMF DMSO“Naked”anions are highly reactive both as bases and nucleophiles(裸露的负离子具有很强的亲核性裸露的负离子具有很强的亲核性和碱性和碱性).在在偶极溶剂偶极溶剂中亲核性顺序中亲核性顺序:F-Cl-Br-I-(与碱性顺序一致与碱性顺序一致)对对SN2反应，偶极溶剂比质子溶剂有利反应，偶极溶剂比质子溶剂有利 6.61,3002,8005,000200,000Relative reactivityH2ODMSODMFCH3CNHMPASolvent3)Sterically hindered nucleophiles are poor ones(位阻大的试剂亲核性差位阻大的试剂亲核性差)亲核性顺序：亲核性顺序：CH3O-CH3CH2O-(CH3)2CHO-(CH3)3CO-(与碱性顺序相反与碱性顺序相反)very easyvery difficultSN28.2.1.2.4 The solvent effects(溶剂效应溶剂效应)溶剂对溶剂对SN2和和SN1均有影响，但对均有影响，但对SN1影响程度更大影响程度更大SN1Polar protic solvent will greatly increase the rate of ionization of an alkyl halide in the above SN1 reaction(对于对于中性底物中性底物,溶剂极性溶剂极性增强增强,使使SN1反应速度反应速度显著加快显著加快).1450Water29Ethanol/water(50%:50%)10Ethanol/water(80%:20%)1EthanolRelative rateSolvent对于对于带正电的底物，带正电的底物，溶剂极性溶剂极性增强，增强，将使将使SN1速率速率有所降低有所降低 0.32Water0.62Ethanol/water(80%:20%)1EthanolRelative rateSolventSN2溶剂极性溶剂极性增强增强，常使，常使SN2速率速率有所降低有所降低 溶剂极性溶剂极性增强增强，将使，将使这类这类SN2速率速率显著加快显著加快 溶剂极性溶剂极性增强增强，将使，将使这类这类SN2速率速率显著降低显著降低 溶剂极性溶剂极性增强增强，使，使这类这类SN2速率速率有所降低有所降低 亲核性强亲核性强 易与正离子结合易与正离子结合 SN1 versus SN21）一卤甲烷，伯卤代烷一卤甲烷，伯卤代烷容易发生容易发生SN2，叔卤代烷叔卤代烷容易发生容易发生SN1，仲卤代烷仲卤代烷可以可以发生发生SN2 或或SN1。烯丙型卤、苄基卤烯丙型卤、苄基卤容易发生亲核取代，容易发生亲核取代，乙烯型卤、芳基卤乙烯型卤、芳基卤不不易发生亲核取代易发生亲核取代2）Ag+(常用常用硝酸银硝酸银或或氰化银氰化银)的作用：促使的作用：促使SN1反应发生反应发生3）两位负离子）两位负离子(Ambident anion)：4）I-既是一个好的离去基团又是一个好的亲核试剂既是一个好的离去基团又是一个好的亲核试剂5）强）强的的亲核试剂亲核试剂有利于有利于SN27）溶剂）溶剂的影响的影响6）好）好的的离去基团离去基团对对SN1及及SN2均有利均有利(对对SN1更有利更有利)质子溶剂质子溶剂的的极性增强极性增强(即即酸性增强酸性增强)有利于常见的有利于常见的SN1质子溶剂质子溶剂的的极性增强极性增强(即即酸性增强酸性增强)不利于不利于常见的常见的SN2偶极溶剂偶极溶剂有利于有利于SN28.2.2 Elimination(消除反应消除反应)E1 and E2SN versus E1)伯卤代烷伯卤代烷碳上无支碳上无支链链时时主要主要发发生生SN2,但是当使用但是当使用非常非常强强的碱的碱(如如NH2)时则时则主主要要发发生生E2碳上碳上有有支支链链时时主要主要发发生生E2 使用大体使用大体积积的的强强碱碱(如如t-BuO)时时主要主要发发生生E22)叔叔卤卤代代烷烷碱性条件碱性条件下主要下主要发发生生E1；溶溶剂剂解解(如如水解，醇解水解，醇解)时时主要主要发发生生SN13)仲仲卤卤代代烷烷弱碱性的弱碱性的强强亲亲核核试剂试剂(如如I,CN,SH,NO2,RCO2)有利于有利于SN2强强碱碱(如如RO)有利于有利于E2;体体积积越大越大,碱性越碱性越强强越有利于越有利于E2碳碳上有支上有支链链，有利于，有利于E2溶溶剂剂解解(如如水解，醇解水解，醇解)时时可以可以发发生生SN1/E14)升温升温有利于有利于E5)偶极溶偶极溶剂剂有利于有利于SN2,极性溶极性溶剂剂有利于有利于SN160%40%13%87%9%91%?8.2.3 Neighboring-group Participation(邻基参与邻基参与)构型翻转构型翻转 SN2 构型保持构型保持构型翻转构型翻转 构型再次翻转构型再次翻转 邻基参与邻基参与促进离去基团的离去，反应速度促进离去基团的离去，反应速度显著加快显著加快参与基团参与基团常带有常带有孤对电子或孤对电子或电子电子The reaction is 3200 times faster!mustard gas(芥子气芥子气)苏式苏式苏式外消旋体苏式外消旋体赤式赤式赤式内消旋体赤式内消旋体赤式赤式赤式赤式(构型保持构型保持)8.2.4 Reduction(还原还原)1)LiAlH4RI RBr RCl RFCH3X 1 2 3(主要发生消除主要发生消除)乙烯基卤乙烯基卤,芳基卤芳基卤也可被还原也可被还原氢化铝锂氢化铝锂还原性强还原性强,可还原可还原醛醛,酮酮,酰氯酰氯,酸酐酸酐,羧酸羧酸,羧酸酯羧酸酯得到得到醇醇;还原还原酰胺酰胺,腈腈,脂肪族硝基化合物脂肪族硝基化合物得到得到胺胺;还原还原炔炔得到得到烯烯2)NaBH4硼氢化钠硼氢化钠活性不如氢化铝锂活性不如氢化铝锂,可在水可在水,醇中使用。可还原醇中使用。可还原醛醛,酮酮,酰氯酰氯得到得到醇醇3)Metal(Sn,Zn,Fe)and acid 可还原可还原卤代烃，卤代烃，还可还原还可还原硝基化合物硝基化合物,腈腈,得到得到胺胺4)HI 5)Catalytic hydrogenolysis(催化氢解催化氢解)可对可对活泼卤代烃活泼卤代烃,如如苄基卤苄基卤,烯丙基卤烯丙基卤进行氢解。还可还原进行氢解。还可还原酰氯酰氯,羧酸酯羧酸酯,醛醛,酮酮得到得到醇醇;还原还原酰胺酰胺,腈腈,脂肪族硝基化合物脂肪族硝基化合物得到得到胺胺;还原还原炔炔,烯烯得到得到烷烷;还原还原苯苯得得到到环己烷环己烷6)Na/NH3(l)双键构型不变双键构型不变还可还原还可还原炔炔得到得到烯烯;对对苯环苯环进行进行Birch还原还原8.3 Preparation8.3.1 Halogenation of hydocarbons(烃的卤化烃的卤化)8.3.2 Addition of halogens or hydrogen halides to alkenes or alkynes(卤素或卤化氢对烯或炔的加成卤素或卤化氢对烯或炔的加成)8.3.3 Preparation from alcohols(由醇制备由醇制备)8.3.4 Preparation from other alkyl halides(由其它卤代烷制备由其它卤代烷制备)8.3.5 Preparation from carbonyl compounds(由羰基化合物制备由羰基化合物制备)机理机理8.3.6 Preparation via haloform reaction(由卤仿反应制备由卤仿反应制备)MechanismIodoform reaction:Acid-catalysed halogenation can be made to stop after one halogen is introduced if only one equivalent of halogen is used.They invented a tool to make carbon-carbon bonds in organic chemistry The tool is called palladium-catalyzed cross-coupling It has applications in a range of fields from medicine to electronicsThe Nobel Prize in Chemistry 2010 was awarded jointly to Richard F.Heck,Ei-ichi Negishi and Akira Suzuki for palladium-catalyzed cross couplings in organic synthesis.Organometallic Compounds(有机金属化合物有机金属化合物)CM bond CNa and CK bonds are largely ionic in character.CPb,CSn,CTl,and CHg bonds are essentially covalent.CLi and CMg bonds lie in between these two extremes.strong base powerful nucleophile8.4 Organicmetallic NomenclatureThe metal is the parentTetramethyllead四乙基铅四乙基铅Methyllithium甲基锂甲基锂Diethylmagnesium二乙基镁二乙基镁Ethynylsodium乙炔乙炔(基基)钠钠Methylmagnesium iodide Diethylaluminum chloride碘化甲基镁碘化甲基镁 氯化二乙基铝氯化二乙基铝 Cyclopropyllithium环丙基锂环丙基锂四甲基硅烷四甲基硅烷 三甲基硼烷三甲基硼烷 三甲基乙基锡烷三甲基乙基锡烷8.5 Preparation8.5.1 Via reaction of organic halides with metals(通过卤代烃与金通过卤代烃与金属反应属反应)Ether(醚醚)：乙醚：乙醚 四氢呋喃四氢呋喃(THF)8.5.2 Via reaction of organometallics with salts(通过有机金属与无通过有机金属与无机盐反应机盐反应)金属的电正性越强，卤素的电负性越强，二者越易成盐金属的电正性越强，卤素的电负性越强，二者越易成盐电正性电正性:Li+Mg2+Al3+Si+4 Zn2+Cd2+H+Sn2+Cu+Hg2+8.5.3 Via reaction of organometallics with hydrocarbons(通过有机通过有机金属与烃反应金属与烃反应)8.6 Organomagnesium Reagents Grignard Reagents(有机镁试有机镁试剂剂格氏试剂格氏试剂)Francois Auguste Victor Grignard(1871-1935)the Nobel Prize for Chemistry in 1912His work in organomagnesium compounds opened a broad area of organic synthesis.8.6.1 Preparation of Grignard reagents Reactivity of halides:RI RBr RCl乙烯型卤，芳基卤乙烯型卤，芳基卤活性不如活性不如卤代烷卤代烷 8.6.2 Reactions of Grignard reagents8.6.2.1 As bases Grignard reagents with acidic hydrogens(格氏试剂格氏试剂作为碱与酸性氢的反应作为碱与酸性氢的反应)HX RSO3H RCOOH H2S H2O RSH ROH RCCH NH3 RNH2 RCONH28.6.2.1 Grignard reagents as nucleophiles(格氏试剂作为亲核试剂格氏试剂作为亲核试剂的反应的反应)1)与与二氧化碳二氧化碳反应反应2)与与活泼卤代烃活泼卤代烃偶联偶联RX应为应为伯卤代烷伯卤代烷,苄基卤苄基卤,烯丙基卤烯丙基卤3)其他底物其他底物碱性碱性条件下条件下环氧化合物环氧化合物开环为开环为SN28.7 Organolithium Compounds(有机锂有机锂)反应：有机锂类似格氏试剂，但活性更高反应：有机锂类似格氏试剂，但活性更高8.8 Organocopper Reagents Lithium Dialkylcuperates(R2CuLi)(有机铜试剂有机铜试剂二烃基铜锂二烃基铜锂)8.8.1 Preparation of R2CuLi8.8.2 Reaction of R2CuLi:Coupling with Alkyl Halo(与卤代烃偶联与卤代烃偶联)乙烯基卤，芳基卤乙烯基卤，芳基卤亦可顺利与二烃基铜锂反应亦可顺利与二烃基铜锂反应链状仲卤代烷，叔卤代烷链状仲卤代烷，叔卤代烷可能发生可能发生消除消除羟基，羧基，羰基羟基，羧基，羰基不受影响不受影响乙烯基卤乙烯基卤的的双键构型双键构型不改变不改变8.9 Organozinc Reagents(有机锌试剂有机锌试剂)Simmons-Smith reaction stereospecific8.10 Organosodium Reagents(有机钠试剂有机钠试剂)Wrtz反应反应an antifungal(抗真菌的抗真菌的)compound isolated from lily plants3-甲基甲基-1,5-二甲氧基二甲氧基-2,4-二氯苯二氯苯2,4-dichloro-1,5-dimethoxy-3-methylbenzeneChlortetracycline氯四环素氯四环素Thyroxine甲状腺素甲状腺素Aryl Halides(芳基卤，卤代芳烃芳基卤，卤代芳烃)8.11 Structure8.12 PreparationHalogenation of arenes(芳烃的卤化芳烃的卤化)Halogenation of aryl diazonium salts(重氮盐的卤化重氮盐的卤化)SN1CuCl CuBrKINaBF48.13 Reactions8.13.2 Formation of Organometallic Reagents(有机金属试剂有机金属试剂)8.13.1 Electrophilic aromatic substitution(芳香族亲电取代芳香族亲电取代)Wrtz-Fittig反应反应Ullmann反应反应Wrtz反应反应Fittig反应反应8.13.3 Nucleophilic Aromatic Substitution(芳香族亲核取代反应芳香族亲核取代反应)SN2 is not reasonable because the aromatic ring blocks backside approach of the nucleophile.Inversion is not possible.SN1 is also unlikely because:1)CCl bond is strong;therefore,ionization to a carbocation is a high-energy process2)Aryl cations are highly unstableNucleophilic aromatic substitution by Addition-Elimination:the SNAr MechanismSuccessful nucleophilic substitution:1)a good nucleophile,such as RSH,HO-,NC-,R2NH,etc;2)a good leaving group,such as halides;3)an electron-withdrawing group ortho or para to the leaving group.SNAr Mechanism：Addition-EliminationStarting from benzene,how to synthesize 4-nitrobenzonic acid(对硝基苯对硝基苯甲酸甲酸)and 4-nitrobenzonitrile(对硝基苯甲腈对硝基苯甲腈)?Reaction rate:X=I Br Cl FReaction rate:X=F Cl Br I尽管尽管芳基卤芳基卤不易发生不易发生SN2与与SN1，但在，但在强碱强碱作用下可以发生亲核取作用下可以发生亲核取8.13.4 Nucleophilic aromatic substitution through an Elimination-Addition mechanism:the Benzyne mechanism(芳香族亲核取代反应的芳香族亲核取代反应的消去消去-加成加成机理机理苯炔机理苯炔机理the orbitals of benzyne(苯炔苯炔)normal bondtwo p orbitalsinside the ringabnormal bondtwo sp2 orbitalsoutside the ringEvidence for benzyne as an intermediate:Regioslectivity(区域选择性区域选择性)取代基取代基(CF3,OMe)即使有孤对电子，也不可能与苯环负离子上的负电共轭即使有孤对电子，也不可能与苯环负离子上的负电共轭（因为（因为p轨道不可能共平面），故只考虑诱导效应。轨道不可能共平面），故只考虑诱导效应。Typical Benzyne Reactions(苯炔的典型反应苯炔的典型反应)SummaryReactions of alkyl halides SN1 SN2 E1 E2ReductionOrganometallicsGrignard ReagentsOrganocopper ReagentsAryl nucleophilic substitutionBenzyne