有机化学课件--第五章 卤代烃

1、RX （ X = F, Cl, Br, I）RClRBrRI,RFRCH2XCHXRRCXRRRCXRRXCXRRCRXRCRRCRXXCH3CH2CH2CH2Br正正溴溴丁丁烷烷CH3CH2CHBrCH3仲仲溴溴丁丁烷烷CH3CBrCH3叔叔溴溴丁丁烷烷CH3正正丁丁基基溴溴仲仲丁丁基基溴溴叔叔丁丁基基溴溴CH3CHCH2BrCH3异异丁丁基基溴溴异异溴溴丁丁烷烷三三氯氯甲甲烷烷氯氯仿仿, , chloroformn-butyl bromidesec-butyl bromidetert-butyl bromideisobutyl bromideCHCl3选取选取含卤素的最长碳链含卤素的最长碳

2、链为主链为主链CH3CH2CHCH2CH3CH2Br2 乙乙基基 1 溴溴丁丁烷烷CH2CH2CCH2CH3CH3HBr(S) 3 甲甲基基 1 溴溴戊戊烷烷CH2ClCl反反 1 氯氯甲甲基基 4 氯氯环环己己烷烷CH3ClCHCH3CH2CH3(R) 2,3 二二甲甲基基 3 氯氯戊戊烷烷CH3HCNOFClBrISP2.12.53.03.54.02.12.53.02.82.5CX CF3CCl3 ,（强强）吸吸电电子子基基团团(electron withdrawinggroup)CRC Cl CRCClClCl CXCX+CXCX+Nu Nu( SNNucleophilic Substi

3、tution Reaction)CHRWW: 吸吸电电子子基基（electron withdrawing group）有有弱弱酸酸性性B（碱碱）CRW+HB CHRCH X BCRCH +X+HB消消除除 H成成烯烯烃烃Elimination Reaction) ）NuRX+XRNu+NuRX+XRHNu+H底物底物 (substrate)亲核试剂：亲核试剂： 至少含有一至少含有一对未共用电子对对未共用电子对OHORSHSROHRORRSHRSRR醇醇醚醚硫硫醇醇硫硫醚醚OCOROCORR酯酯NuR+XRNuCNCCR炔炔基基负负离离子子CNRCCRR腈腈高高级级炔炔丙丙二二酸酸酯酯负负离离子

4、子CH(CO2Et)2R烷烷基基丙丙二二酸酸酯酯IIRCH(CO2Et)2NuR+XRNu碘碘代代烷烷HOHHORHNH2HNHRHNR2NR3(水)(醇)(氨)(伯胺)(仲胺)(叔胺)ROH醇醇ORR醚醚RNH2伯伯胺胺RNHR仲仲胺胺RNR2叔叔胺胺RNR3 X季季铵铵盐盐NuR+XRHNu RX为重要有机中间体为重要有机中间体（intermediates）RXORRSHRSRROCORRCNRCC RRCH(CO2Et)2RIRNaOH or H2ONaOR or HORNaSH or NaSRNHR2(H)CCRNaCCRXMgorNaCH(CO2Et)2NaCNNaIRCOONa酯酯

5、腈腈高高级级炔炔烷烷基基丙丙二二酸酸酯酯醇醇醚醚伯伯胺胺仲仲胺胺叔叔胺胺硫硫醇醇( (硫硫醚醚) )OHRNH2RNHRRNR2R碘碘代代物物NuXRNuRXNuRX+过过渡渡态态NuRX+NuRXNuXR+势势能能反反应应进进程程 XRRNuNuR势势能能反反应应进进程程XRXRRX+NuRX+慢慢快快 动力学证据动力学证据反应速率反应速率立体化学证据立体化学证据对手性底物，对手性底物，产物的立体化学产物的立体化学重排重排现象现象反应类型反应类型I I RXNu构型翻转构型翻转无无双分子机理双分子机理bimolecular mechanismIIII RX消旋化消旋化有有单分子机理单分子机理

6、unimolecular mechanismNuRX+XR+NuC6H13H3CBrH+NaOHC6H13CH3HOH+NaBr构构型型发发生生转转换换与与 SN2 机机理理吻吻合合C6H13H3CBrHOHC6H13CCH3BrHHO C6H13CH3HOH+Br仲仲卤卤代代烷烷R1R2XR3Nu+R1R2NuR3R1R2NuR3+叔叔卤卤代代烷烷与与 SN1 机机理理吻吻合合R1R2XR3R1R2R3 XNuR1CR2NuR3()卤代烷亲核取代的两种机理：卤代烷亲核取代的两种机理： SN2 和和 SN1 机理机理(CH3)3CF+(CH3)3CSbF6可可通通过过核核磁磁共共振振观观察察到

7、到SbF5超超酸酸R2CHR3C1o2o3oCH3sp2 杂杂化化平平面面型型RCH2RHRH+RR+e 键键离离解解能能 电电离离能能RHRH+e 3o2o1oCH33o2o1oCH3,PhCH2CH2=CHCH2 H (KJ/mol)13161130100010719701040CHRCH2RRCCH pCHRORCHRORCHXRCHXRppppCHCHHH2CH pCHHH p（诱导）吸（诱导）吸CCF3CCCl3CCOCNO2CCH2HHH3CH2CCCH2H3CH2CHHHCCH2HH3CH2C HCCH2CH3HH3CH2CCCH2H3CH2CCH3H HCCHCH3CH3CH3

8、H3C CH3CCHCH3CH3CH3H3CCH3CH2Br+NaOHCH3CH2OHNaBr+CH3CH2BrOHCH3CH2OH+Br 希望通过这些例子，学习并基本掌握反希望通过这些例子，学习并基本掌握反应机理的表达方法应机理的表达方法CH3CBrCH3CH3+H2O乙乙醇醇CH3COHCH3CH3HBr+CH3CBrCH3CH3CH3CCH3CH3H2OBrCH3COHCH3CH3CH3COHCH3CH3+HBrHBrCCH2BrCH3CH3H3CCCH2OC2H5CH3CH3H3CC2H5OHCCH2CH3CH3OC2H5H3C+AgNO3 CH3CCH2CH3CH3H3CBrCCH2

9、CH3CH3H3C AgBrCCH2CH3CH3H3CC2H5OHCCH2CH3CH3H3CC2H5ONO3CCH2CH3CH3OC2H5H3C HNO3HAgNO3 绝对的按绝对的按 SN2 或或 SN1 机理的例机理的例子不多，一般情况下两种机理并存，子不多，一般情况下两种机理并存，并依反应条件而改变。并依反应条件而改变。NuRX+XR+Nu溶溶剂剂l R的结构的结构l CX键键强度强度l 体积体积l 浓度浓度l 亲核能力亲核能力 l 浓度浓度l 对亲核试剂的影响对亲核试剂的影响l 对反应的影响对反应的影响l 稳定性稳定性XRRNuNuRX慢慢快快NuXR NuRX+CX键强度：键强度：

10、F Cl Br ICX键易解离键易解离CX键易解离键易解离相对相对速率速率相对相对速率速率空间位阻效应空间位阻效应 电子效应电子效应BrROHRBr+OH80%乙醇水溶液55oCCH3CHH3CBrCH3CH3CCH3BrCH2H3CBr1000.220BrH3C7.99BrRIRNaBr+NaIAcetone（丙丙酮酮）CH3CHH3CBrCH3CH3CCH3BrCH2H3CBr1500.010.001BrH3C1相对相对速率速率BrROC2H5RBr+OC2H5无无水水乙乙醇醇55oCCH2H3CBrCH2CH2BrCH2CHBrCH2CBrH3CH3CH3CCH3H3CCH3100283

11、 0主要原因：主要原因：空间位阻效应空间位阻效应相对相对速率速率相对相对速率速率正碳离子稳定性正碳离子稳定性空助效应（消除空助效应（消除X减少基团拥挤）减少基团拥挤）BrROHRHBr+H2O80%乙乙醇醇- -水水55oCCH2H3CBrCH3CHH3CBrCH3CH3CCH3Br1000.0230.0140BrH3CBrROHRHBr+H2OHCOOHCH2H3CBrCH3CHH3CBrCH3CH3CCH3Br108451.71.0BrH3CHOC2H5OC2H5RClRIRNaCl+NaIAcetoneCH3CHH3CClCH2CH2ClH3CCH2H3CClCH2CHClH2CCH3C

12、lCH2Cl1.03393930.00760.37l 苄基与烯丙基苄基与烯丙基卤代烃卤代烃易发生易发生SN2相对相对速率速率l 相对相对速率速率ClROHRHCl+H2O80%乙乙醇醇- -水水HOC2H5OC2H5RCH3CHH3CClCH2H3CClCH2CHClH2CCH2Cl1.0CH3CH3CCH3ClHORNH2NH3FH2OR3CR2NHFRONH2ROROIBrClRSROHSHO,质子性溶剂中质子性溶剂中OSH3CCH3OCHNCH3CH3CH3CNOCH3CCH3DMFDMSO(Dimethyl Sulfoxide)(N, N Dimethylformamide)二二甲甲亚

13、亚砜砜N, N 二二甲甲基基甲甲酰酰胺胺ROH H2O RCOOHH2OHCOOHCH3OHC2H5OHCH3COOH805933246DMSODMFCH3CN49373621CH3CCH3OFClBrIRSROHSHOFHOHHOHHHOHHOCXNu 正离子被溶剂化了，正离子被溶剂化了，负离子完全释放出来。负离子完全释放出来。负负电荷密度大者亲核性较强电荷密度大者亲核性较强（与碱性顺序一致）。（与碱性顺序一致）。如：如： MX 在在 DMSO 中中OSH3CCH3MOSCH3H3COSCH3CH3OSH3CH3CXFClBrI强强弱弱free大体积大体积弱亲核弱亲核性强碱性强碱大体积大体积

14、碱强碱碱强碱强强弱弱强强弱弱亲核性亲核性试剂的体积作用试剂的体积作用烷基给电子作用烷基给电子作用碱碱 性性OCCH3CH3H3COCHCH3H3COCH2H3COH3CLDA (Lithium Diisopropyl Amide)NCHCH3H3CCHH3CCH3LiDIEA碱碱性性亲亲核核性性(CH3)2CH2NC2H5(C2H5)3N弱弱强强强强弱弱NuXRNuRX NuRX+XRRXXR X+极性大：极性大：对极性大（电荷密度集中）体系有利。对极性大（电荷密度集中）体系有利。极性小：极性小：对极性小（电荷密度分散）体系有利。对极性小（电荷密度分散）体系有利。SN2 机理机理SN1 机理机

15、理电荷密度集中电荷密度集中（极性大）（极性大）电荷密度分散电荷密度分散（极性减小）（极性减小）极性较小极性较小极性增加极性增加低极性溶剂对稳低极性溶剂对稳定过渡态有利定过渡态有利极性溶剂对稳定极性溶剂对稳定过渡态有利过渡态有利XR：1o ， 2oNu：强强亲亲核核性性， 大大浓浓度度溶溶剂剂：非非质质子子性性， 低低极极性性XR：3o, 烯烯丙丙型型, , 苄苄基基型型Nu：弱弱亲亲核核性性（避避免免SN2）溶溶剂剂：大大极极性性对对SN2有有利的因素利的因素对对SN1有有利的因素利的因素典型的典型的SN2典型的典型的SN1L = F, Cl, Br, INuRL+LR+Nu强强弱弱10-2

16、1 50 150FClBrI溶于丙酮溶于丙酮碘离子的碘离子的高亲核高亲核性性和和好离去性好离去性ClRNu, NaIIRNuR NaINu溶解性能的差别溶解性能的差别Cl ( Br)RNaI丙丙酮酮IR+NaCl (NaBr)不溶于丙酮不溶于丙酮SN2C6H13H3CIHNa I*丙丙酮酮消消旋旋化化光光学学纯纯a. 消旋化速率取决于消旋化速率取决于RI和和I b. 消旋化速度比同位素交换快一倍消旋化速度比同位素交换快一倍2. 试解释下列实验现象试解释下列实验现象（Hughes，1935）1. 由丙烯制备烯丙基碘由丙烯制备烯丙基碘H2CCHCH3H2CCHCH2I醇的羟基难取代醇的羟基难取代R

17、OHNuRNu+OHROC2H5RNH2RCN均难被取代均难被取代例：醇的溴代例：醇的溴代SN2 or SN1金属的络合物金属的络合物SN2 or SN1ROHHBrROH2BrRBr+H2OROHHClRHOZnCl2ClRCl +HOZnCl2ZnCl2SN2H3CSOOClH3CSOOORH3CSOOOROTsTsClOTs稳定的负离子，弱碱稳定的负离子，弱碱ROHTsClROTsNuRNuOTs+ HCl试写出合理的机理解释试写出合理的机理解释CH3HPhOHTsClCH3HPhOTsC2H5OKCH3HPhC2H5OCH3HPhOHKCH3HPhOKC2H5OTsCH3HPhOC2H

18、5 一般情况下，消除一般情况下，消除与亲核取代反应同时与亲核取代反应同时存在（竞争）存在（竞争） Elimination Reaction)取代反应，取代反应，SN2 or SN1X+Nu CHRCH X BCRCH +X+HBCHRCHNu 弱碱弱碱强碱强碱注意：注意：主要产物的结构主要产物的结构 有何特点？有何特点？CH3CH2CH2CH2ClCH3CH2CHCH2CH3CH2CHCH3ClCH3CH2CHCH2CH3CHCHCH3+主主要要次次要要CH3CH2CCH3BrCH3CH2CCH2CH3CHCCH3+主主要要次次要要CH3CH3CH3 EtOHKOHEtOHKOHEtOHKOH

19、EtOH注意：注意：消除为立消除为立 体专一性体专一性PhH3CHBrHPh PhCH3HBrHPh orKOEtEtOHCCH3CPhHPhPhH3CHBrHPh PhCH3HBrHPh or1R, 2R1S, 2S1S, 2R1R, 2SKOEtEtOHCCH3CPhHPh动力学证据动力学证据反应速率反应速率反应的立体化学反应的立体化学重排重排现象现象反应类型反应类型I I RXB:立体专一性立体专一性无无双分子机理双分子机理IIII RX无选择性无选择性有有单分子机理单分子机理 CHRCH X BCRCH +X+HB+ CCHXBCC+BHCCHXB + X五中心过渡态五中心过渡态势势能

20、能反反应应进进程程SPTCCHXCCH XB CC+BH慢慢快快SPT1T2M势势能能反反应应进进程程 CCHXBCC+BHCCHXB + XCCHXCCH XB CC+BH慢慢快快CCHX CH3CH2CHCH3ClCH3CH2CHCH2CH3CHCHCH3+主主要要次次要要 EtOHKOHCHClCH2CH3CHHHOHabCH3CHCHCH3CH3CH2CHCH2ab+H2O+Cl+H2O+ClCH3CH2CCH3BrCH3 CCH2CH3CHHHCH3 BrBrabaCH3CHCCH3CH3bCH3CH2CCH2CH3+HBrHBr+CH3CH2CCH3BrCH3CH2CCH2CH3C

21、HCCH3+主主要要次次要要CH3CH3CH3 EtOHKOHCH3CH2CCH3BrCH3CH2CCH2CH3CHCCH3+主主要要次次要要CH3CH3CH3 EtOHCCH3CHCH3BrCH3H3CEtOHCCCH3CH3H3CCH3+CCHCH3CH3H2CCH3CH3CCHCH3BrCH3H3C BrCCH3CHCH3CH3H3C CH3(CH3 迁迁移移)CCCH3CH3H2CCH3H BrCCCH3CH3H3CCH3H BrCCHCH3CH3H2CCH3abba CH3CH2CCH3BrCH3CH2CCH2CH3CHCCH3+主主要要次次要要CH3CH3CH3EtOHCH3CH2

22、CHCH3ClCH3CH2CHCH2CH3CH+主主要要次次要要EtOHKOHCHCH3E2 机理机理E1 机理机理为什么？为什么？CCRRRRCCRRHRCCRHHRCCRRHHCCRHHH CCHHHHCCRHHRCCRHHR有有 van der waals 排斥力排斥力CC+催催化化剂剂CCHH H = 氢氢化化热热（放热）H2+ H2+ H2+ H2CH3CH2CHCH3ClCH3CH2CHCH2CH3CH+主主要要次次要要EtOHKOHCHCH3E2 反应反应CHClCH2CH3CHHHOHabCH3CHCHCH3CH3CH2CCH2abCH3CHCHCH3ClHHO ClHOH C

23、H3CH2CHCH2E1 反应反应CH3CH2CCH3BrCH3CH2CCH2CH3CHCCH3+主主要要次次要要CH3CH3CH3EtOHCH3CH2CCH3BrCH3 CCH2CH3CHHHCH3 BrBrabaCH3CHCCH3CH3bCH3CH2CCHCH3CH3CHCCH3CH3HBr HBr CH3CH2CCH2CH3CH3(CH2)3CHCH3ClCH3(CH2)3CHCH2CH3(CH2)2CHCHCH3+CH3OCH3CH3CCH3O67%9%33%91%ROZaitsev 取向取向Hofmann 取向取向H3CCCH2CCH3BrCH3CH3CH3H3CCCH2CCH2CH

24、3CH3CH3H3CCCHCCH3CH3CH3CH3+C2H5OCH3CH3CCH3O98%86%14%2%RO CCHXBCCHXB CCHXB HXB sp3 sp2CCHXBCCHXB CCB HXB HX重叠式构象，重叠式构象，较不稳定。较不稳定。负电荷相距较近，负电荷相距较近，有排斥作用有排斥作用PhH3CHBrHPh PhH3CHBrHPhEtOCCH3CPhHPhHPhCH3HPhBrEtOPhH3CHBrHPh PhCH3HBrHPh orKOEtEtOHCCH3CPhHPh(H3C)2HCClCH3C2H5O(H3C)2HCCH3(H3C)2HCClCH3C2H5O(H3C)

25、2HCCH3(H3C)2HCCH3+75%25%唯唯一一产产物物III消除速率消除速率I : II = 200 : 1(H3C)2HCClCH3(H3C)2HCClCH3HHHC2H5O(H3C)2HCCH3Hab(H3C)2HCCH3baIOC2H5(H3C)2HCClCH3(H3C)2HCClCH3HHH(H3C)2HCClCH3HHHC2H5O(H3C)2HCCH3HIICCXHNuB1o2o3oRXCH3CHCHCH3CH3BrNaI丙丙酮酮CH3CHCHCH3CH3ICH3CCHCH3CH3CH3CHCHCH3CH2CH3CHCHCH3CH3BrCH3COONa丙丙酮酮CH3CHCH

26、CH3CH3OCOCH3CH3CCHCH3CH3CH3CH CHCH3CH2CH3CCH3CH3Cl80% C2H5OH20% H2OCH3CCH3CH3OHCH3CCH3CH3OC2H5H2CCCH3CH3+CH3CCH3CH3BrCH3CCH3CH3OC2H5H2CCCH3CH3+C2H5ONaC2H5OH分析分析：醚类化合物可：醚类化合物可由亲核取代制得由亲核取代制得Williamson 醚合成法醚合成法切断切断(disconnection)CH3CCH3CH3OCH3RX+O RROR亲亲核核取取代代(Retrosynthetic analysis)RORRX+O RCH3CCH3CH

27、3OCH3abaCH3CCH3CH3X+OCH3bCH3CCH3CH3OXCH3+有两种切断方式有两种切断方式哪一种更有合成意义？哪一种更有合成意义？CH3CCH3CH3XHOCH3NaNaOCH3H2CCCH3CH3CH3CCH3CH3OICH3CH3CCH3CH3OHNaCH3CCH3CH3OCH3Hofmann取向取向 CCHFBCC+BHFCCF 慢慢快快机理：经过碳负离子中间体机理：经过碳负离子中间体CH3CH2CH2CH2CHCH3FCH3ONaCH3OHCH3CH2CH2CH2CHCH2CH3CH2CH2CHCHCH3+70%30%C F键较强键较强不易断开不易断开CH3CH2C

28、H2CHFCH3CH2CH2CHCHCH2FHHCH3OOCH3abCH3CH2CH2CH2CHFabCHCH3CH2CH3CH2CH2CH2CHCH2CH3CH2CH2CHCHCH3 F F较稳定较稳定较不稳定较不稳定Hofmann取向的解释取向的解释2o1oCCFOC2H5DCCHFOC2H5CCDFCCHFDOC2H5CCDFOC2H5 /机理机理RXLiAlH4NaBH4（还还原原 2o or 3o RX）Zn / HClNa / NH3 (液液)H2 / PdRHXR还还原原剂剂CH3R 合成上合成上若涉及还原若涉及还原反应，应注反应，应注意底物中是意底物中是否有卤素。否有卤素。RX

29、+Mg醚醚RMgXXMgXMgOR2RRR2ORXMgORRORR单单体体( (稀稀溶溶液液) )二二聚聚体体( (浓浓溶溶液液) )烷基卤化镁烷基卤化镁Grignard试剂试剂（溶解于醚）（溶解于醚）RX+2 Li醚醚或或烷烷烃烃RLi+LiX烷基锂烷基锂R XLi+R XLi+R XRX+R+LiR Li有机金属化合有机金属化合物物金属与金属与碳直接成键碳直接成键常用醚：常用醚：乙醚乙醚四氢呋喃四氢呋喃（THF）O RMgXR2CdR2CuLiRLi烷基锂烷基锂烷基卤化镁（烷基卤化镁（Grignard试剂，格氏试剂，格林雅试剂）试剂，格氏试剂，格林雅试剂）二烷基铜锂二烷基铜锂烷基镉烷基镉R

30、M （M = 金金属属，metal）金属金属电负性电负性Li1.0Mg1.2Cd1.7Cu1.9较活泼金属可与较活泼金属可与 RX 直接反应直接反应RX+2 Li醚醚或或烷烷烃烃RLi+LiXRX+Mg醚醚RMgX2 RLi+CuIR2CuLi+LiI2 RMgCl+CdCl2R2Cd+2 MgCl2较不活泼金属，用交换法较不活泼金属，用交换法反应活性：反应活性：RI RBr RCl脂肪族脂肪族卤代物卤代物 芳香族芳香族卤代物和卤代物和烯基烯基卤代物卤代物Victor Grignard(1871 1935)诺贝尔化学奖诺贝尔化学奖（1912）RX+Mg醚醚RMgX现制现用现制现用RMgX R RMgX+2ROMgX2O2H2OROH化合物化合物pKa共轭碱共轭碱化合物化合物pKa共轭碱共轭碱(CH3)3C H71(CH3)3CH2N H36H2NCH3CH2 H62CH3CH2