郑州大学 有机化学6炔烃 二烯烃

1、enediyne antibiotic (烯二炔抗生素烯二炔抗生素)Not only do enediynes inhibit cell growth, they have a greater tendency to kill cancer cells than they do normal cells. The mechanism by which enediynes act involves novel chemistry unique to the CC-C=C-CC unit .The enediyne group is often called a warhead because i

2、t is ready to cyclize, forming benzene via a highly reactive 1,4-dehydrobenzoid diradical intermediate. Chapter 6 Alkynes and DienesAlkynes(炔烃炔烃)CCsp-hybridized6.1 Structure, Isomerism and Nomenclature (结构结构,异构和命名异构和命名)StructureElectronegativity(电负性电负性)：CspCsp2Csp3The acidity of the C-H bonds increa

3、ses.The CC bond becomes shorter and stronger. IsomerismHC CC CH3CHC CNomenclatureCommon namesC CHH3CC CH3CC2H5C CHCHH2C甲基乙炔甲基乙炔 甲基乙基乙炔甲基乙基乙炔 乙烯基乙炔乙烯基乙炔IUPAC names-ane -yneHC CC CH3CHC C1-戊炔戊炔 2-戊炔戊炔 3-甲基甲基-1-丁炔丁炔C CH3CC CH3CH3CH34,4-二甲基二甲基-2-戊炔戊炔4,4-dimethyl-2-pentyneC CH3CH2C CHHCCH3ClCH35-甲基甲基-6-氯

4、氯-2-庚炔庚炔6-chloro-5-methyl-2-heptyne同时含有双键和三键的分子同时含有双键和三键的分子1)选择含有双键和三键的最长碳链作为主链选择含有双键和三键的最长碳链作为主链2)从离双键或者三键最近的一端开始编号从离双键或者三键最近的一端开始编号 (编号时使烯炔编号之和最小编号时使烯炔编号之和最小)HC C(E)-3-戊烯戊烯-1-炔炔(E)-3-penten-1-yne(Z)-3,6-庚二烯庚二烯-1-炔炔(Z)-3,6-heptadien-1-yne3) 当烯炔编号之和同样大小时，使烯的编号最小当烯炔编号之和同样大小时，使烯的编号最小H3C CC C C CH3HH(E

5、)-2-己烯己烯-4-炔炔(E)-2-hexen-4-yneCl(2Z,5S)-5-甲基甲基-5-氯氯-2-辛烯辛烯-6-炔炔(2Z,5S)-5-chloro-5-methyl-2-octen-6-yne4-乙烯基乙烯基-1-庚烯庚烯-5-炔炔4-vinyl-1-hepten-5-yne1-甲基甲基-2-炔丙基环己烯炔丙基环己烯1-甲基甲基-2-(2-丙炔基丙炔基)环己烯环己烯 1-methyl-2-(2-propynyl)cyclohexene12347565-乙炔基乙炔基-1,3,6-庚三烯庚三烯5-ethynyl-1,3,6-heptatrieneBrCClC14顺顺-1-氯乙炔基氯乙炔

6、基-4-溴环己烷溴环己烷 cis-1-bromo-4-chloroethynylcyclohexaneAlkynyl groups(炔基炔基)HC CC CH3CHC CH2C乙炔基乙炔基 丙炔基丙炔基 炔丙基炔丙基 1-丙炔基丙炔基 2-丙炔基丙炔基6.3.1 Acidity of terminal alkynes (末端炔烃的酸性末端炔烃的酸性)HCCHCCHHHHHCCHHHHHpKa = 25pKa = 44pKa = 50RHR- + H+Carbanion (碳负离子碳负离子)Conjugate base (共轭碱共轭碱)HF HSH HOH HOR HCCR HNH2 HCH=C

7、H2 HCH2CH3Relative acidity (相对酸性相对酸性)Basicity of conjugate base (共轭碱的碱性共轭碱的碱性)Relative stability of anion (负离子的相对稳定性负离子的相对稳定性)6.2 Physical Properties (物理性质物理性质)6.3 Reactions (反应反应)a very weak acid an exceptionally strong base HA + B-HB + A-(stronger acid) (stronger base)(weaker acid) (weaker base)NH

8、3，醇有时称为碱有时称为酸，为什么？，醇有时称为碱有时称为酸，为什么？NH3 + H2ONH4+OH-NH3 + CH3LiCH4LiNH2+RCCH + RMgX RCCMgX + RHRCCH + n-BuLi RCCLi + n-BuHHCC: Na+ + CH3Br HCCCH3RCCH + Ag(NH3)2+RCCAg(白白)RCCH + Cu(NH3)2+RCCCu(红棕红棕)CN-RCCHFormation of metal alkynides (金属炔化物的形成金属炔化物的形成)HCCH + NaNH2 liq. NH3 HCC: Na+ + NH3RCCH + LiNH2 l

9、iq. NH3 RCC: Li+ + NH3Addition to carbony compounds (与羰基化合物的加成与羰基化合物的加成)HCCH + CH2OKOHpressHCC-CH2OHCH2O / KOHpressHOCH2-CC-CH2OHKOHCH3CCC H + CH3COCH3CH3CC-C-CH3OHCH3Mechanism(机理机理)RCC-B-RCCC HO+_RCC-O-CCROHCCRHalogenation of terminal alkynes(末端炔烃的卤代末端炔烃的卤代)RCCH + HOBr RCC-Br + H2O6.3.2 Reduction o

10、f alkynes (炔烃的还原炔烃的还原)Catalytic hydrogenation(催化氢化催化氢化)CH3CCCH3PtH2CH3CH=CHCH3PtH2CH3CH2CH2CH3syn addition Lindlars catalystCCquinolineLindlars catalystCCHRHRRRH2+Reduction with Na or Li in liquid NH3 (用金属钠或金属锂在液氨用金属钠或金属锂在液氨中还原中还原)CC(CH2)2CH3CH3(CH2)21)Na / NH3(l), -78oC2)NH4ClCC(CH2)2CH3HHCH3(CH2)2

11、anti addition Mechanism Radical anion(自由基负离子自由基负离子)Vinylic radical(乙烯基自由基乙烯基自由基)Reduction with LiAlH4 (用氢化铝锂还原用氢化铝锂还原)CCCCHHLiAlH4anti addition 6.3.3 Hydroboration (硼氢化反应硼氢化反应) CCCCBHBH3 / THF3H2O2 / OH-RCOOHC CHOHC CHH氧化氧化还原还原Keto(酮式酮式)Enol (烯醇式烯醇式)OHHsyn additionAnti-Markovnikov addition Tautomeri

12、sm(互变异构互变异构)C COC COHHCH3(CH2)5CCHBH3 / THFCH3(CH2)5CHCHB3H2O2 / OH-CH3(CH2)5CHCHOHCH3(CH2)5CH2CHORCOOHHHHCH3(CH2)56.3.4 Electrophilic addition (亲电加成亲电加成) C CE+C CEA-C CEAEAAAEE1）活性：活性：炔烃的亲电加成比烯烃炔烃的亲电加成比烯烃困难困难，并且可以与两分子试剂加成（第二步，并且可以与两分子试剂加成（第二步的加成更困难），如控制试剂用量则的加成更困难），如控制试剂用量则可以使反应停留在一分子加成产物可以使反应停留在一分

13、子加成产物上。上。2）区域选择性：区域选择性：加成取向遵循加成取向遵循马氏规则马氏规则3）立体化学：立体化学：大多是大多是反式加成反式加成Addition with HX(与卤化氢加成与卤化氢加成)gem-dihalide(偕二卤代物偕二卤代物)CCCCXHCCHHXXHXHXHC CHHClHgCl2150160+CH2CHClC CC2H5HHI+C2H5IHHHIC2H5CIICH3C CC2H5C2H5HCl+C2H5ClC2H5HReactivity of alkynes (炔的活性炔的活性): RCCR RCCH HCCHReactivity of hydrogen halides

14、 (卤化氢的活性卤化氢的活性): HI HBr HClRegioselectivity(区域选择性区域选择性): Markovnikovs ruleStereochemistry(立体化学立体化学): anti addition (反式加成反式加成)Peroxide effect(过氧化物效应过氧化物效应) C CH +HBrperoxideperoxideHBrn-Bun-BuCH=CHBrn-BuCHCH2BrBrn-BuCBr=CHn-BuC=CHBrn-BuCHCHBrBrn-BuCHCHBr2Vic-dibromide(邻二溴代物邻二溴代物)Addition with X2(与卤素加

15、成与卤素加成)CCCCXxCCXXXXX2X2Stereochemistry (立体化学立体化学): anti addition (反式加成反式加成)Reactivity of halogens (卤素的活性卤素的活性): F2Cl2Br2I2+ Br2(1mol)CH C CHCH2CH CH2CCHCH2+ Br2(1mol)BrHC CBrCH2CH2CH CH2CHCCH2BrBrAddition with H2O (与水加成与水加成)Regioselectivity(区域选择性区域选择性): Markovnikovs rule (马氏规则马氏规则)Enol to Keto (in A

16、cid)Enol to Keto (in Base)tautomerization互变异构互变异构6.3.5 Oxidation of alkynes (炔烃的氧化炔烃的氧化)RCCR1. KMnO4, OH-2. H+RCO2HRCO2H+RCCR1. O32. HOAcRCO2HRCO2H+6.3.6 Nuleophilic addition of alkynes (炔烃的亲核加成炔烃的亲核加成)H H C CCHHCNCuClCH2=CHCNROHbaseCH2=CHORH H C CCHRCOOHCH2=CHOCORH H C CCH6.3.7 Polymerization of al

17、kynes (炔烃的聚合炔烃的聚合)HC CH2CuCl / NH4ClH2C CHC CH500H H C CCCu2ClC CH HXXbase, - HXC CC CH XXHHXbase, - HX6.4 Preparation of alkynes (炔烃的制备炔烃的制备)C CMRR_X+C CRRBimolecular nucleophilic substitution(双分子亲核取代双分子亲核取代): SN2发生两次发生两次E2反应，第二次更困难反应，第二次更困难v = k卤代烷卤代烷 金属炔化物金属炔化物 + -Must be 1alkyl halide (the alkyl

18、ating agent烷基化试剂烷基化试剂) 6.4.1 Dehydrohalogenation of dihalides (二卤代物脱卤化氢二卤代物脱卤化氢)CH3CH2CHCH2BrBrNaNH2mineral oilCH3CH2CHCHBrCH3CH2CCH2Br+H3CH2CCCHCH3CH2CCNaNH4ClC3H3CH2CCH110-160 oCNaNH2mineral oil110-160 oCNaNH2CCH3OPCl50oCC1) NaNH22) H+mineral oilheatCCH3ClClCH46%ClHNaNH2 / NH3(l)Benzyne(苯炔苯炔)CH3CH

19、2CHCHCH2CH3Cl ClKOH / alcoholCH3CH2C CCH2CH3Molten KOH or alcoholic KOH at 200 C favors an internal alkyne.Sodium amide, NaNH2, at 150 C, followed by water, favors a terminal alkyne.(熔融的熔融的氢氧化钾或者氢氧化钾醇溶液常使炔键移向氢氧化钾或者氢氧化钾醇溶液常使炔键移向链中链中，而氨基钠使炔键移，而氨基钠使炔键移向向链端链端)Migration of Triple Bond (三键的迁移三键的迁移)6.4.2 A

20、lkylation of metal alkynide (金属炔化物的烷基化金属炔化物的烷基化)HCCH + NaNH2 liq. NH3 HCC: Na+ + NH3RCCH + LiNH2 liq. NH3 RCC: Li+ + NH3RCCH + RMgX RCCMgX + RHRCCH + n-BuLi RCCLi + n-BuHHCC: Na+ + CH3Br HCCCH3C CMRRX+C CRRSN2 (双分子亲核取代双分子亲核取代)The alkylating agent (烷基化试剂烷基化试剂) must be 1alkyl halideRCC -CBrCRHHRHRCCH

21、+ RCHCHR + Br-2o Alkyl halideE2C C HHHHCH3H3C设计由乙炔合成反设计由乙炔合成反-2-丁烯的路线丁烯的路线Retrosynthetic Analysis (逆合成分析逆合成分析) CCHCH3H3CHH3CCCCH3HCCCH3anti-additionCCCH3H3CH2+H3CCC -Na+CH3I+HCC -Na+CH3I+HCCH1. NaNH2/liq. NH32. CH3IHCCCH3H3CCCH1. NaNH2/liq. NH32. CH3IH3CCCCH3CCCH3H3C1. Li,EtNH22. NH4ClTMForward Synt

22、hesis (正向合成正向合成)Protects against:Strokes (中风中风)coronary thrombosis (冠状动脉血栓冠状动脉血栓)hardening of the arteries (动脉硬化动脉硬化)Allicin (大蒜素大蒜素)Conjugated dienes(共轭二烯烃共轭二烯烃)孤立二烯烃孤立二烯烃共轭二烯烃共轭二烯烃累积二烯烃累积二烯烃丙二烯类化合物丙二烯类化合物1245636145231,3-Cyclohexadiene 1,4-Cyclohexadiene Allene not conjugatedCCCdebaCCCdebasp hybrid

23、6.5 Structure and Physical Properties of Conjugated Dienes (共轭共轭二烯的结构和物理性质二烯的结构和物理性质)CH2=CH-CH=CH2 1,3-丁二烯丁二烯rotate aboutC2C32323s-cis conformations-trans conformationWhich is more stable, why?6.5.1 ,-conjugation (,-共轭共轭)存在于共轭体系存在于共轭体系 无限远无限远交替极化交替极化键长平均化键长平均化电子离域电子离域稳定性增强稳定性增强2,3-Di-tert-butyl-1,3-

24、butadiene behaves like a nonconjugated dienesH2CCH2Bu-tt-BuCCCH2C(CH3)3H2C(H3C)3CH2CCHCH2CH2CHH2CCH2CHH2CH2CCHCH2CH2CHH2CH2CCHCH2H2CCHC H2+H2CCHC H2H2CCHC H2-6.5.2 The molecular orbital theory (分子轨道分子轨道理论理论)Linear combination of atomic orbitals (LCAO原子轨道线性组合原子轨道线性组合)1)The MOs that are formed encompa

25、ss all the nuclei, and, in them, the electrons can move about all the nuclei (形成的分子轨道包围着所有的原子核，在分子轨形成的分子轨道包围着所有的原子核，在分子轨道中电子围绕着所有的原子核运动道中电子围绕着所有的原子核运动).2)The MOs may contain a maximum of two spin-paired electrons (每个分子轨道每个分子轨道最多容纳两个自旋方向相反的电子最多容纳两个自旋方向相反的电子).3)The number of MOs that result always equ

26、als the number of AOs that combine (分子轨道的数目总是等于参与组合的原子轨道的数目分子轨道的数目总是等于参与组合的原子轨道的数目).反键轨道反键轨道成键轨道成键轨道The MOs in the ethene (乙烯的分子轨道乙烯的分子轨道)The MOs in the 1,3-butadiene (1,3-丁二烯的分子轨道丁二烯的分子轨道)Highest Occupied Molecular Orbital最高占有轨道最高占有轨道Lowest Unoccupied Molecular Orbital最低未占轨道最低未占轨道The overall energy

27、 of the two bonding butadiene molecular orbitals is lower than that of the two molecular orbitals for ethene. This means that butadiene is more thermodynamically stable than we might expect if its structure were just two isolated double bonds (丁二烯两个成键分子轨道的总能量低于两个乙烯分子轨道的能量。这意味着丁二烯在热力学上比两个孤立的双键稳定)The

28、HOMO for butadiene is higher in energy relative to the HOMO for ethene. This means butadiene should be more reactive than ethene towards electrophiles (丁二烯的最高占有轨道的能量比乙烯高。这意味着丁二烯比乙烯更易与亲电试剂反应)The LUMO for butadiene is lower in energy than the LUMO for ethene. Consequently, butadiene would be expected

29、to be more reactive towards nucleophiles than ethene (丁二烯的最低未占轨道的能量比乙烯低。因此，丁二烯比乙烯与亲核试剂的反应活性更高)So whilst butadiene is more stable than two isolated double bonds, it is also more reactive (因此，虽然丁二烯比两个孤立的双键稳定，其反应活性更高)Points to notice:The MOs in the allyl system (烯丙基体系烯丙基体系)烯丙基正离子烯丙基正离子烯丙基自由基烯丙基自由基The n

30、onbonding molecular orbital must be the HOMO of the molecule but is also the LUMO since it still has room for one more electron. It is actually called the Singly Occupied Molecular Orbital (SOMO). The shape of this orbital tells us that the single electron is located on the end carbon atoms.烯丙基负离子烯丙

31、基负离子6.6 Reactions of Conjugated Dienes (共轭二烯的反应共轭二烯的反应)6.6.1 Aaddition with X2 or HX (与卤素或卤化氢加成与卤素或卤化氢加成)Br215oCCH2BrCHBrCH=CH2 + CH2BrCH=CHCH2Br(55%)(45%)CH2=CHCH=CH2Br260oCCH2BrCHBrCH=CH2 + CH2BrCH=CHCH2Br(1%)(99%)CH2=CHCH=CH21,2-additiondirect addition 1,4-additionconjugate addition BrBrBr2CHCl3(

32、68%)CH2CHCHHBr+80oC40oCCH3CHCHCH2Br(80%)CH3CHCHCH2Br(20%)CH3CHCHCH2(20%)Br+CH3CHCHCH2(80%)Br+40oCCH21,2-addition1,4-additionBr Br CH3CHCHCH2BrCH3CHCHCH2Br1,2 Product1,4 ProductMechanism CH3CHCHCH2kinetic control(动力学控制动力学控制)thermodynamic control(热力学控制热力学控制)The thermodynamic product is the most stable

33、 product (热力学产物是最热力学产物是最稳定的产物稳定的产物).The thermodynamic product predominates when the reaction is reversible(thermodynamic control) (当反应可逆时当反应可逆时,热力学产物占主导热力学产物占主导,即即反应受热力学控制反应受热力学控制).The kinetic product is the product that is formed most rapidly(动力学产物动力学产物生成得最快生成得最快).The kinetic product predominates w

34、hen the reaction is irreversible (kinetic control) (当反应不可逆时当反应不可逆时,动力学产物占主导动力学产物占主导,即反应受动力学控制即反应受动力学控制).Higher temperature favors the formation of the thermodynamic product(高温有利于热力学产物的生成高温有利于热力学产物的生成).Thermodynamic Versus Kinetic Control(热力学控制与动力学控制比较热力学控制与动力学控制比较)6.6.2 Addition with H2 (与氢加成与氢加成)CH

35、2=CH-CH=CH2H2 / Ni1,2-addition 1,4-additionCH3CH2CH2CH3使用使用Na / NH3 (l)，则主要发生则主要发生1，4-加成加成H2 / Ni6.6.3 The Diels-Alder ReactionSynthetic method for preparing compounds containing a cyclohexene ringtransition statetransition state diene(二烯二烯)Dienophile(亲二烯体亲二烯体)Otto Diels and Kurt Alder won the Nobel

36、 Prize for Chemistry in 1950 for developing this reaction.HOHONHCH3HMorphine (M. Gates)OOCH3HHHCH3OHOCH2OHCortisone (R. B. Woodward)NNHMeOHHMeO2CHOMeOOMeOOMeOMeReserpine (R. B. Woodward)Lets focus on the HOMO and the LUMO of the reactantsfrontier orbitals(前线轨道前线轨道)Electrons flow from the HOMO of the diene to the LUMO of the dienophile (电子从电子从二烯体的二烯体的HOMO流入流入亲二烯体的亲二烯体的LUMO). Influence of the structure of the reactants (反应物结构的影响反应物结构的影响)The diene must adopt the s-cis conformation in the transition s