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1、1,2-DichloroethaneBromomethaneHalothaneDichlorodifluoromethaneDDT a Banned InsecticideDDT the first of the chlorinated organic insecticides, was originally prepared in 1873, but it was not until 1939 that Paul Muller of Geigy Pharmaceutical in Switzerland discovered the effectiveness of DDT as an in
2、secticide he was awarded the Nobel Prize in medicine and physiology in 1948 for this discovery).Dichlorodiphenyltrichloroethane The use of DDT increased enormously on a worldwide basis after World War II, primarily because of its effectiveness against the mosquito that spreads malaria and lice that
3、carry typhus. The World Health Organization estimates that during the period of its use approximately 25 million lives were saved. DDT seemed to be the ideal insecticideit is cheap and of relatively low toxicity to mammals (oral LD50 is 300 to 500 mg/kg). However, problems related to extensive use o
4、f DDT began to appear in the late 1940s. Many species of insects developed resistance to DDT, and DDT was also discovered to have a high toxicity toward fish.In 1962, Rachal Carson wrote “Silent Spring”.The chemical stability of DDT and its fat solubility compounded the problem. DDT is not metaboliz
5、ed very rapidly by animals; instead, it is deposited and stored in the fatty tissues. The biological half-life of DDT is about eight years; that is, it takes about eight years for an animal to metabolize half of the amount it assimilates. If ingestion continues at a steady rate, DDT builds up within
6、 the animal over time. The use of DDT was banned in the United States in 1973, although it is still in use in some other parts of the world. MidazolamDormicum(咪唑安定)R- Haloperidol （氟哌啶醇五氟利罗（Penfluridol）口服20160mg/15天。毒性低安全系数为100%，对各类分裂症均有效。 ）3R-X(X:Cl,Br,I)脂肪卤烃芳香卤烃饱和卤烃RCH2X2R2CH-X3R3C-X不饱和卤烃R-CH=CH-X(
7、vinyl)R-CH=CH-CH2X(allyl)1RCH2-X6.1 Classification and nomenclature1.ClassificationVinylic halideAllylic halide2. Nomenclature. A.Commonnames:Alkyl+fluoride;chloride;bromide;iodidePhenyl bromideB.TheIUPACnames:Rulesaresimilartothatofhydrocarbons.(1)Thelongestcarbonchaincontaininghalogenatomsisnameda
8、sthebasechain,alkylgroupsandhalogensareconsideredassubstituents,whichareindicatedbythelowestpossiblenumber.(2)Iftherearesubstituentsatthesamedistancefrombothends,beginnumberingattheendnearerthesubstituentwithalphabeticalpriority.3)Forthealkenes,thedoublebondisgiventhelowestpossiblenumber.6.2 Chemica
9、l propertyBond length(nm) 0.139 0.176 0.194 0.214Bond energy(kJ/mol) 456 351 293 243CX bond is easy to be broken.Reaction type: Nucleophilic substitution, elimination, reaction with metals+-CXpolarcovalentbond(极性共价键)RCHCH2H+SN.E.ClLeaving groupNucleophilesubstrate6.2.1. Nucleophilic substitution rea
10、ctionNucleophilic SubstitutionReactionsRX + Y-RY + X-RCH2X+NuRCH2-Nu+X(底物）substrate(亲核试剂）N.reagent(离去基）leavinggroupRCCNa+RCH2-CCRNaIRCH2-INaOHRCH2-OHNaCNRCH2-CNRONaRCH2-ORAgONO2RCH2-ONO2(AgX)(离子型)ExamplesH3O+RCH2COOH*N.reagentNH3RCH2-NH2RNH2RCH2-NHRR-OHRCH2-OR(中性)H2ORCH2-OHNuor:NuExamplesn-BuBr + Na
11、OEtn-BuOEt + NaBrReaction of n-butyl bromide with sodium ethoxide in ethanol at 55oC.n-BuBr + NaOEtn-BuOEt + NaBrReaction of n-butyl bromide with sodium ethoxide in ethanol at 55oC.n-BuBr + NaOEtn-BuOEt + NaBrRate=kn-BuBrNaOEtBoth n-BuBr and NaOEt are in the transition state.Displacement from FRONT
12、or BACK?HOW TELL IF INVERSION OR RETENTION?+Nu-ORRetentionInversionReactionCoordinateEnergyTransitionStateS N 2 Mechanism：LNuLNuLNuLNuLNuLNuLNuLNuLNuLNuInversion of configuration (构型转化构型转化)Walden inversionNu:L+ L-NuStereochemistry of reaction构型构型翻转翻转(R) - (-) - 2 -Bromooctane25D= -34.25Purity of ena
13、ntiomer=100%(S) - (-) - 2 - Octanol25D= -9.90对映体的纯度对映体的纯度=100%SN2SubstitutionNucleophilic2 Bonds at a timebimolecular reaction MeBrEtBri-PrBrt-BuBr221,0001,3501very smallRelative ReactivityRelative Reactivity under SN2 Conditions1.00.80.0360.00002What is the mechanism of this reaction?HinderedNaOEtS
14、N1SubstitutionNucleophilic1 Bond at a timeunimolecular reaction Reaction CoordinateEnergyTransition StateIntermediatet-BuXi-PrXEtXMeX1243100,000,000Relative Reactivity in Formic Acid Solvent - SN1Stereochemistry of SN1MethylEthylIsopropylt-ButylLog RateSN2SN1* 双分子亲核取代反应双分子亲核取代反应 SN2:* Mechanism* Ste
15、reochemistry立体化学：立体化学：Walden转化转化,构型翻转构型翻转反应活性反应活性: 1 2 3影响因素影响因素: 空间位阻空间位阻* 单分子亲核取代反应单分子亲核取代反应 SN1* Mechanism*Stereochemistry立体化学：对映异构体的混合物立体化学：对映异构体的混合物反应活性反应活性: 1 2 3影响因素影响因素: a) 电性因素电性因素碳正离子：碳正离子：SP2杂化杂化碳正离子的稳定顺序碳正离子的稳定顺序:R3C R2CH RCH2 CH3+通过烷基的通过烷基的 -P超共轭效应：超共轭效应：四面体四面体平面三角型平面三角型键角增大，键角增大，取代基空间取
16、代基空间效应越大，效应越大，基团的空间基团的空间拥挤程度减拥挤程度减小。小。b) Steric effectFactors Influencing Mechanism of Substitution*Structure of substrate*Concentration and activity of nucleophile*Solvent effect 电子效应电子效应空间效应空间效应(Steric effect)Inductive effect (诱导效应）诱导效应）Conjugative effect (共轭效应）共轭效应）R-X = CH3X 1 2 3SN1SN2（空间位阻减小，（
17、空间位阻减小，SN2反应程度增加）反应程度增加）（空间位阻加大，（空间位阻加大，SN1反应程度增加）反应程度增加） 影响反应机理和活性的因素：影响反应机理和活性的因素：（1） 底物结构：底物结构：立体效应立体效应电性效应电性效应烷基烷基-R离去基离去基-L影响：影响： 对对 SN1 大于大于 SN2碱性弱的基团，离去能力强碱性弱的基团，离去能力强.卤代烷的反应活性：卤代烷的反应活性：RI RBr RCl RF 碱性碱性: I - Br - Cl - F - 离去能力离去能力: I - Br - Cl - F -(2 ) 亲核试剂：亲核试剂：强亲核试剂：强亲核试剂： SN2弱亲核试剂：弱亲核试剂
18、：SN1NuNu-: CH3O-, HO-, I-Nu: H2O:Nu:在在 SN2反应中起着重要作用反应中起着重要作用lThe nucleophile can be neutral or negatively charged as long as it has an unshared pair of electrons. So it is also a Lewis base（路易斯碱）路易斯碱）. lBasicity (碱性碱性) how well the base shares electrons with a proton.lNucleophilicity (亲核性亲核性) how re
19、adily the nucleophile is able to attack an atom (e.g. carbon) other than a proton. EnglishtextbookP130l由于在由于在 SN1 反应中，亲核试剂是在限速反应中，亲核试剂是在限速步骤发生后才进入反应，因此，不影响步骤发生后才进入反应，因此，不影响反应速率反应速率l进而，可以预计中性亲核试剂与负离子进而，可以预计中性亲核试剂与负离子的亲核试剂一样有效，所以，的亲核试剂一样有效，所以，SN1 反应反应常在中性或酸性条件下进行。常在中性或酸性条件下进行。（3） 溶剂：溶剂：非极性：苯，非极性：苯，CCl
20、4, CS2极性极性:非质子性极性溶剂非质子性极性溶剂 DMSO, DMF 等等质子性极性溶剂：乙醇等质子性极性溶剂：乙醇等极性极性 溶剂可以稳定正离子溶剂可以稳定正离子,也可稳定负离子。也可稳定负离子。Solvent EffectsAcetic AcidMethanolFormic AcidWater145,000150,000Relative reaction rate of t-butyl chlorideSN1Polar solvents favor charge developmentSolvent Effects on SN2 Reactions with Anions171,30
21、02,8005,000proticproticaproticaproticaproticSN 1 reaction： 一个中性化合物离解为两一个中性化合物离解为两个带电荷的离子，溶剂极性个带电荷的离子，溶剂极性的提高，将稳定正碳离子，的提高，将稳定正碳离子，使反应速率加快。使反应速率加快。SN 2 reaction： 在过渡态中不产生新的电荷，而且还使电荷分在过渡态中不产生新的电荷，而且还使电荷分散，溶剂的极性增加，不利于电荷的分散，使反应散，溶剂的极性增加，不利于电荷的分散，使反应速稍有降低。速稍有降低。What type of reaction is this?SN2What type o
22、f reaction is this?SN1Most reactive in SN2 reaction?CH3CH2CH2BrMore reactive in SN1 reaction?(CH3)3CBrFaster solvent for the SN1 reaction of t-butyl chloride?WaterEthanolWaterActivityofalkylhalides(differentstructuresofalkylgroups)烯丙式卤三级卤代烷二级卤代烷一级卤代烷乙烯式卤SummarySubstitution ReactionsMechanism of SN1
23、and SN2 reactionsRelative Reactivity in SN2Primary Secondary TertiaryRelative Reactivity in SN1Tertiary Secondary PrimarySolvent Effects SN1 and SN2 reactionsKineticsSterochemistryPreparation of AlkenesC-CXYTo make C=C need to eliminate X, Y.C-CXY3 ways to break 2 bonds1. Concerted (x and y leave sa
24、me time)2. X leaves first3. Y leaves firstDehydrohalogenationC-CXHStrong baseR-XR+X-Alkene + H+E1 ReactionE1Elimination1 bond at a timeMechanism of E ( unimolecular, bimolecular reaction)(1)E1- C - C -XHSlow- C - C -H B:Fast-X- C = C - + H B R+SubstitutionEliminationRearrangementSN1E1(2) E2Activity
25、of E1 and E2 Activity: 321E1:3RX3C+E2:3RX产生的烯烃稳定产生的烯烃稳定一致一致Element EffectChange ElementIBrClOrientation81%19%Get more stable alkeneC=CRHAlkyl groups here stabilize double bond In dehydrohalogenation the preferred product is the alkene that has the greater number of alkyl groups attached to the doubl
26、e-bonded carbon atoms.Saytzeff Rule:NaOEtWhat is the major product of this reaction?NaOEt71%29%Example6%94%+What type of reaction is this?E1What type of reaction is this?E2RXSN2/E2（亲核性强、亲核性强、Nu浓）浓）SN1/E1 （亲核性弱，亲核性弱，Nu稀）稀）10SN2为主。若为主。若RX或或Nu有空阻，则有空阻，则E2占占优。优。不能进行不能进行SN1/E1反应反应20SN2/E2二者均可。碱二者均可。碱性越强、碱体积越大、性越强、碱体积越大、温度越高，温度越高，E2越有越有利。利。SN1/E1二者均可。温二者均可。温度越高，度越高，E1越有利。越有利。30Only E2SN1/E1二者均可。温二者均可。温度越高，度越高，E1越有利。越有利。E2/E1, S/E竞争问题竞争问题Grignardreagent6.2.3 Reaction with metals乙烯卤和芳卤不活泼，要制得Grignard试剂，须改变溶剂，提高温度。烯丙式卤和苄卤较活泼，要低温反应Grignard试剂与活泼氢的反应
