第一章--有机化学-卤化反应

第一章卤化反应HalogenationReaction定义：有机化合物分子中引入卤素原子(X)的反应称卤化反应。用途：制备特定活性化合物制备官能团转化的中间体引入卤素原子作为保护基、阻断基等OCH3COOHOCH2ICOOHOCH2OCCH3COOHI2/CaOCH3OH/CaCl2OCH3COOKDMF定义：分子中形成C-X的反应特点：引入卤原子可改变有机分子中的性质，同时能转化成其它官能团。如：制备药物中间体糖皮质激素醋酸可的松制备具有不同生理活性的含卤素的有机药物H2NCCCH2OHHOHHNHCOCHCl2氯霉素诺氟沙星COOHFC2H5NHNO亲电加成亲电取代亲核取代自由基反应（取代，加成）不饱和烃的卤加成反应卤取代反应卤置换反应卤化反应中的重排反应类型:第二节不饱和烃的卤加成反应和卤素的加成反应和次卤酸(酯)的加成反应和N-卤代酰胺的加成反应和卤化氢的加成反应和硼烷的加成反应及卤解第二节不饱和烃的卤加成反应概述1.加卤素2.卤内酯化3.加卤化氢CCX2CCXXX2=Cl2,Br2CCHXCCHXHX=HCl,HBr,HICH2COOHOOII2/KI/NaHCO34.次卤酸，N-卤代酰胺反应5.硼氢化－卤解反应CCX2CCOHX+H2OHXX2=Cl2,Br2+CH3CH=CH2CH3CHBrCH3CH3CH2CH2Br无过氧化物过氧化物Markovnikov加成反Markovnikov加成第二节不饱和烃的卤加成反应一、不饱和烃加卤素1X2对烯烃的加成F＞CI＞Br＞IF与不饱和烃反应太剧烈CH2=CH2+Br2→BrCH2CH2Br+CI2→CICH2CH2CI+I2→ICH2CH2I机理：亲电加成溶媒：CH2CI2CHCI3CCI4CS2CCCCXXX2ccccccｘｘ+R1R2R3R4R1R2R4R3R3R4R2R1①反向ｘｘｘｘ+-R1R2R4R3R3R4R2R1②正向ｘｘ+-ccccｘδδ-ｘ机理:CCArHCH3HBr2CCArHCH3HBrCCArHCH3HBrBrCH2=CH2(CH3)2C=CH2HOOCCHCHCOOH比较下面六个化合物的活性(CH3)2C=C(CH3)2CH3CH=CH2CH2=CHCN立体化学问题CH3HCH3H+Br2BrCH3HCH3H+Br(a)(b)(a)(b)CH3HCH3HBrBrCH3HCH3HBrBrCH3HBrBrHCH3CH3BrHHBrCH3Cl2ClHHClClHHCl+Br2BrHHBrBrHBrH+与Cl2加成产物同向加成,因为Cl不易形成桥环MeHOMeBrBrHOMeClClHOBr2Cl2CCH3CHHC2H5H3CHHC2H5H3CHHC2H5CCCCClClClOAc+AcOH/LiClCl2CH3-CH=CH2CH3-CH-CH2IOHI2/KIO393%HIHOAcI2/AcOAg2、卤素对炔加成得反式二卤烯烃C-CH3CphC-CH3CphCCphC-CH2OHCBrBrClClCH3Br2LiBrCl2CCIHCH2OHII2二、不饱和酸卤内酯反应CH2COOHOOII2/KI/NaHCO3CCOCHHPhBr2BrPhOOOH第二步三、不饱和烃和次卤酸（酯），N-卤代酰胺的反应机理实例CCR1R3R2R4CCR1R3R2R4CCR1R3R2R4OHXOHXX-OHHClOHBrOCl--OHBr--OHRROHClRClOHHOCl+Ar-CHCH2COClHClO水中(有机溶剂中)AcOH收率较低Ar-CH-CH270%Ar-CH-CH2OH-Cl+ClOHOEtOt-BuOCl/ROHOEtOClROHOEtOClOROOOROHBrHOBrPh-CH=CH2Ph-CH-CH2OHBrNBANBS英文名称：N-Bromosuccinimide别名：N-溴代琥珀酰亚胺。结构式：NCSNBANCACH2-CCHt-BuOClH3CCOCH2ClH3CCCHClOHArCCHArCOCH2Clt-BuOCl1HX对烯烃的加成CCR1R2R4R3CCR1R2R4R3HXCCR1R2R4R3XHHX++HClClCH3-CH=CH2CH2-CHCH3ClHCl只有HBr有反马氏规则Ph-CH=CH2HBrHBrH2O2或光照Ph--C-CH3Ph-CH2CH2BrBr反马氏规则四、卤化氢对不饱和烃的加成反应机理CCR1R2R3R4H+CCR1R2R3R4HNuNuCCR1R2R3R4NuCCR1R2R3R4NuHH反向同向反马氏规则机理HBrHBr光+CCBrRRHH+CCRRHHBrCCRHHHBrBrHHBr2HX对炔烃得加成CH2-CCHHClH3CCCH2ClCH3-CH=CH2BH3(CH3-CH2-CH2)3BBr2/CH3ONaCH3CH2CH2Br反马氏产物C6H13CCHOBHO70℃,2hCCC6H13HHOBO25℃,2hCCC6H13HHB(OH)2CCC6H13HHI90%I2/NaOH/H2OEt2O/0℃H2O五、硼烷的加成第三节烃类的卤代反应炔烯丙位苄位C2H6BrC2H5BrCH2CH2BrBr2CHCH2BrCH4CH3Cl(g)CH2Cl2CHCl3CCl4ArCCHI2/NaOHArCCArCCHII-HIICH2=CH-CH3CH2=CH-CH2BrNBSAr-CH3Ar-CH2BrNBS一、脂肪烃的卤取代反应机理（自由基)例NOOXX+CH3-CH=CH-RCH2-CH=CH2-RHXXCH2-CH=CH-R+NOOXNOOX+hor过氧化物CH3(CH2)3CH=CH-CH3CH3-(CH2)2-CH-CHBrNBS/(PhCO)2O2CCl4/△,2hCHCH3HCCH3CHCHBrCHCHClNBSNCS/CH3CH2BrNBSNCSCH2ClCH2CH2CH3CHCH2CH3NBSBrNCH3NCH2ClNCH2BrNBSNCS+CH2CH2COOHCHCH2COOHBrNBSAr-CH3Ar-CBr3Ar-COOH3Br2水解CH3CH3CHBr2CHBr2CHOCHO4Br2/光水解合成脂肪族羧酸合成芳醛机理例+E+E慢π-络合物HEE+H+σ-络合物快HHXX-H+X+-X-σ-络合物Cl2/FeClCH3+CH3CH3ClCH3ClCH3CH3BrClBr+2molBr2/Fe+二、芳烃卤代反应（亲电取代）1molBr2/CS2OHOHBr°0COHBrBrBrH2O3Br2H2O2Br22Br2/Bu-NH2-70COHBrBrOHBrBr°OHOHOHOHOHBrBr2/CS2CH3CH3OHOHCH3Br2CH3BrNO2NO2Br2/FeNO2ClBrNH2ClCF3SO2OClHNO2FKFNH2NH2BrNBS/DMFCH3NO2COOHNNNOBrBrOHONNNOBrHOHOCH3NO2COOHBr浓H2SO4++NNBr2/H2SO4△BrNNAcOH20～25℃NH2Br2BrNH2NH2NO2NH2NO2II2/Hg(OAc)2第四节羰基化合物的卤代反应O2NC-CH3OO2NC-CH2BrOHBrBr2+氯霉素的制备OCH3OCH3BrBr2OCH3OCH3ClSO2Cl2SOOClClSOClCl二氯硫酰氯化亚砜一、醛酮α-位氢的卤代反应1酮α-H卤代反应OCH3OCH3BrBr2OCH3OCH3ClSO2Cl2(CH3)3CCOCH3(CH3)3CCOCBr3(CH3)3CCOOHHCBr3Br2/NaOH71%-74%酸碱催化的定位问题CCH2CH3H3COCCHCH3H3COBrBr21,3二羰基化合物CCH2CCH3H3COOCCHCCH3H3COOClCF3SO2ClEt3NCCH2CH2CH3H2COHCCHCH2CH3H3COHCCH2CH2CH3BrH2COCCH2CH2CH3H2COHBrBrHBr-Br2CCH2CH2CH3BrH2COCCHCH2CH3H3COBr+(1.5%)(58%)溴对酮的加成Oα-羰基自由基取代OCCOR'HR''R'''+Br2+CCOR'BrR''R'''光Br22Br光O+HBrOHBrOOBrBrBr2副反应OOBrBrBrBrOOHBrBrBrBr+Br+(选择性溴化试剂)选择性溴化剂OOOOBrBrCH3CH3OBrCH3OCH3OCH-ArOCH-ArBr(选择性溴化试剂)5,5-二溴代-2,2-二甲基-4,6二羰基-1,3-二恶烷选择性溴化剂C4H9CHOC3H7-CCHOAc2OC3H7-CH=CH-OAcC3H7CHCHOAcOAc+Br2BrBrH+OOOOBrBrCHOCHOBr2醛α-H卤代反应H3CCHOBrH2CCHOAc2OCH2=CH-O-C-CH3OBrH2CHCOCH3OCH3Br2/MgCH3OH+OAcNBSOBrAcOOAcH2CAcOOBrH2CNBS1烯醇酯的卤化反应二、烯醇和烯胺衍生物的卤化反应第三节羰基化合物的卤代反应OSiCH3CH3CH3ClSiCH3CH3CH3O+Et3NClSiCH3CH3ClSiClSiAr2CH332烯醇硅烷醚卤化反应OSiOBrBr2CCH3BuH2COCCH2BuH2COCCBuHCH3OSiSi+CCH2BrBuH2COCCH3BuHCOBr+Br2-78℃△反应机理例COOEtOHCCOOEtCOOEtBrClSiBr2SiOOHCCHOClSiCOSiHCHOBrBr2等摩尔OSiI2/AcOAgOICOSiCCO-SiCXXCCXOXSi+X-X3烯胺卤化OH3CH3CNNOH3CNHONHororH3COCH3BrNH3CNBr-60℃H3CBrO室温OCH3N-78℃OCH3ClCH3ClCCCl3CCl3O+90%9%叔丁酯是保护羧基的一种方法CH2COOHRCHCOOHRXCHCOOHCC-BrOBr2/PPH3CH3CBrCCOBrOCCOOHBrOHCF3COOHHCl三、羧酸α-H卤代反应第五节醇酚醚的卤素置换反应HI﹥HBr﹥HCl﹥HF叔﹥仲﹥伯ROHRXHXOHClHClCH3-CH2-OHCH3CH2Br△HBr一、醇的卤置换反应1与HX反应第四节醇酚醚的卤素置换反应CH3(CH2)2-CH2OHCH3(CH2)CH2ClHClZnCl2△HBrCH3-CH=CH-CH2OHCH3CH=CH-CH2BrCH3-CH-CH=CH2Br+浓HCl-ZnCl2Lucas试剂第四节醇酚醚的卤素置换反应COHSOCl2COSOClOOSNiOOCOSOClCCl构型保持SN2COSOClC构型反转PyHClClCl-SO2CC外消旋无溶剂ClClSN12与氯化亚砜的反应第四节醇酚醚的卤素置换反应CH3-CH=CH-CH2OHCH3CH-CH=CH3CH3-CH=CH-CH2Cl+0.7molSOCl2/Et2O5.6molSOCl2/Et2OCl76%24%99%1%oCH2OHCH2CloSOCl2Py第四节醇酚醚的卤素置换反应R-OHPX3ROPXXR-XHPXXOHX++CH3CH2CH2OHCH3CH2CH2ClPCl3PCl3(C3H7O)3P亚磷三丙酯NBr2P(Ar)3:Br2P(Ar)3OOHOBr3与卤代磷反应第四节醇酚醚的卤素置换反应Ph3P催化卤化机理优点：反应条件温和。(PhO)3PICH3催化碘化机理：P由三价变为五价，此催化剂往往得构型反转产物Ph3PX2+Ph3PX2+ROHROPPh3X+HXRXPPh3O+(Ph3O)3PICH3(Ph3O)3PCH3X+ROH(PhO)2P-OR+PhOHRIH3CPOIOPhOPh+第四节醇酚醚的卤素置换反应光学纯度80%，得构型反转产物Ph3P/NBS对酸不稳定的醇或甾体醇进行卤代Ph3PX2，(PhO)3PICH3，Ph3P/NBS催化，得构型反转产物ArCCH3HOHPh3PBr