有機(jī)化學(xué)Chap 12(2012-1)課件

Chapter12NitrogenousCompoundsandAlkaloidsSection1AmineⅠ.ClassificationandNomenclatureammoniaprimaryaminesecondaryaminetertiaryamine1quaternaryammoniumsaltquaternaryammoniumhydratetertiaryamineQuaternaryammoniumhydratesarestrongbase.Thebasicityofquaternaryammoniumhydratesaresimilartosodiumhydroxide.季銨鹽季銨堿2胺：有機(jī)非離子型(amine)銨：離子型(ammoniumion)氨：氨水、氨氣或有機(jī)基團(tuán)(ammonia，amino)3Thesystematicnomenclaturenamesaminesanalogouslytoalcohol.Anothermethodnamesaminesassubstitutedalkanes..Thenamesofaromaticaminesarebaseontheparentcompound,calledbenzenamine（苯胺）

bytheofficialworldandaniline(oraminobenzene)byeveryoneelseAminesbearingdifferentRarenamedbyorderingthegroupsalphabetically5methylaminediethylaminetriethylamineBenzylethylmethylamine甲乙芐胺N,N-dimethylaniline61-amino-3-methylbutanebenzyldodecyldimethylammoniumbromideorbromo-geramine,溴化二甲基十二烷基芐基銨新潔爾滅，苯扎溴銨，disinfector（消毒劑）7II.StructureofAmines8Ⅲ.PreparationofAromaticAmineFe/HClcanreducenitrogroupbutcannotreducecarbon-carbondoublebond.Ni,Pd,Pt10Sequenceofthebasicityofamines12鹽酸雙氯醇胺、鹽酸克侖特羅Clenbuterolhydrochloride,Spiropent瘦肉精142.Acylationamide15×16Acetanilidehadbeenusedasantifebric,butitstoxicityistoohigh.Phenacetin非那西丁AcetanilideParacetamol撲熱息痛173.Sulfonylationbenzenesulfonylchloridep-toluenesulfonylchloride18TheabovereactionisnamedHinsbergReaction（興斯堡反應(yīng)）.Usingthisreactioncandistinguishprimary,secondaryandtertiaryamines.Theproductsofprimaryaminesreactwithbenzenesulfonylchlorideisweakacid,socandissolveinsodiumhydroxidesolution.Theproductsofsecondaryaminesarecrystal,andcannotdissolveinsodiumhydroxidesolution.Fortertiaryamines,thisreactioncannottakeplace.204.Reactwithnitrousacid(HNO2)(1)Primaryamines21(3)TertiaryaminesAliphatictertiaryaminesdonotreactwithnitrousacidtogiveanisolableproduct.23emeraldgreensolidActually,weusesodiumnitrite/hydrochloricacidNaNO2/HClinsteadofnitrousacid(HNO2).yellowsolid24SomethingMore:Nitrosoaminesareimportantbecausemanyareknowntobepotentcarcinogens.Thisfindinghasledtoacontroversyovertheuseofsodiumnitrite(NaNO2)asapreservativeinfoodsbecauseitmightbeanitrosatingagentunderphysiologicalconditions,orundertheconditionsinwhichfoodisprepared.Theclassicexampleisthefryingofbacon,whichgeneratesnitrosoamines.However,theevidenceisnotdefinitiveonthispoint.Manyfoods(spinach),evenourownbodies,producenitrites.26N-Nitrosodimethylamine27whiteprecipitation5.SpecialReactionofAniline28Dopamine(DA，多巴胺),thedecreaseofDAwillcauseparkinsonism.30瑞典阿爾維德·卡爾松(ArvidCarlsson)美國保羅·格林加德(PaulGreengard)奧地利埃里克·坎德爾(EricKandel)TheNobelPrizeinPhysiologyorMedicine2000

315-Hydroxytryptamine(5-羥色胺),Serotonine(血清胺)32Melatonin(MLT)褪黑素(又稱松果體素或腦白金)33Fluoxetine(氟西汀)Prozac(百憂解)Areyouprozactoday?34Paroxetine，Seroxat（帕羅西汀，賽樂特）35(S)和(R)-西布曲明36epinephrinenorepinephrineisoprenaline,syntheticmedicine37ephedrinePhenylpropanolamine,PPAN，N-二甲基-γ-(4-氯苯基)-2-吡啶丙胺順丁烯二酸鹽,馬來酸氯苯那敏,撲爾敏38deoxyephedrine,“ice,”apopularpeppill.phenylpropanolamine,PPA39？40CanweuseClemmensenReactiontoreducethecarbonylgroup?Why?Route1:41ClemmensenReactionZn-Hg/HCl:zincamalgam★42Route2:43Ecstasy,3,4-methylenedioxymethamphetamine(MDMA)愛它死,3,4-亞甲二氧基甲基安非他命,快樂丸,E仔,搖頭丸4445PictureofSomeMDMA(Ecstasy)pills

46MDMA在2001年被美國食品藥物管理局（FoodandDrugAdministration；FDA）批準(zhǔn)用于創(chuàng)傷后應(yīng)激障礙（post-traumaticstressdisorder)患者的試驗(yàn)。47Section2DiazoandAzoCompoundsⅠ.DiazotizationReactionbenzenediazoniumchloride0~5℃重氮正離子主要的共振結(jié)構(gòu)：48CH2NN:+.._49Ⅱ.ReactionofDiazoSalt1.Substitution50H3PO2:hypophosphorousacid(次磷酸)512)Howtosynthesize1,3,5-tribromobenzenefrombenzene?Question:1)Howtosynthesize2-methylbenzoicacidfromtoluene?520~5℃1)532)0~5℃542.CoupledReaction(偶聯(lián)反應(yīng))55Azocompoundsareendowedwithcolor,canbeusedasdye.Forexample:methylorange（甲基橙）56（Sudan,蘇丹紅）5758SudanI,Solventyellow14SudanIISudanIIISudanIV59SudanISudanII60SudanIII61SudanIV62Givetheproductsoffollowingreactions:63Section3AmidesⅠ.NomenclatureAmides,thenitrogencounterpartsofesters,aresystematicallynamedbydroppingthefinal“e”oftheparentalkaneandaddingthesuffix“amide.”Asusualthesmallermembersoftheclasshaveretainedtheircommonnames,whicharebaseonthecommonnamesforsmallercarboxylicacids.SubstitutiononnitrogenisindicatedwithaprefixN,asinN-methyl,N,N-diethyl,andsoon.Cyclicamidesareknownaslactams(內(nèi)酰胺).64ethanamideoracetamide3-methylbutanamidebenzamideβαβ-propiolactamN,N-dimethylformamide(DMF)Aall-purposesolvent65Ⅱ.ChemicalProperties1.AcidityandBasicityAlmostamidesareneutral.Aclassicexceptionalexampleisphthalimide,whichisveryweakacid.Question:whyphthalimideisdifferentformotheramides?662.Hydrolysis67WeknowPenicillinGsodiumorpotassiumarestoredinsolidform,andbedispensedtoinjectionbeforebeused.WhyPenicillinGsodiumorpotassiumcannotbepreparedtoinjectioninlaboratories?PenicillinGsodiumorpotassium683.ReactwithNitrousAcid69Ⅲ.ImportantAmides1.UreaChemicalPropertiesofUrea:(1)Slightlybase70(2)Hydrolysis71(3)ReactwithNitrousAcid72(4)BiuretReaction(縮二脲反應(yīng))Biuretcandissolveinalkalisolution.Ifalittlecupricsulfatebeaddedtothebiuretalkalisolution,thecolorofthesolutionwillturntovioletcolor.ThiscolorreactioniscalledBiuretReaction.Compoundscontaintwoormorethantwopeptidelinkages(肽鍵)suchaspolypeptide,protein,etc.cantakeplacebiuretreaction.Peptidelinkages（肽鍵）73三聚氰胺（Melamine）三聚氰酸（Cyanuricacid）742.Sulfonamides(SulfaDrugs,磺胺藥物)p-sulfanilamide,theparentcompoundofsulfadrugsSulfonamidesareantimicrobial.75Prontosil,百浪多息Domagk,1932TheNobelPrizeinPhysiologyorMedicine1939

76Thegeneralstructureofsulfonamides.77sulfamethoxazole(SMZ),orSinomin,磺胺甲噁唑,新諾明trimethyoprim(TMP),三甲氧芐氨嘧啶aexcellentsynergistforsulfadrugsChemitrim(百炎凈):400mgSMZ+80mgTMP783.Guanidine胍guanidino胍基guanyl脒基Guanidineisastrongorganicbase,itsbasicityissimilartopotassiumhydroxide(KOH.)79Someimportantmedicinescontainguanidinoorguanyl.Cimetidine,西咪替丁,甲腈咪胍,泰胃美Ranitidine,雷尼替丁，呋喃硝胺80Famotidine,法莫替丁,高舒達(dá)Cimetidine,RanitidineandFamotidineareHistamineH2-ReceptorAntagonists,usedasanti-gastriculcermedicines.CimetidineisthefirstgenerationhistamineH2-receptorantagonist;RanitidineandFamotidinerespectivelybelongtosecondandthirdgeneration.814.MalonylUrea(丙二酰脲,巴比妥酸)barbituricacidureadiethylmalonate82Thebarbituricaciddoesnotpossessbiologicalactivities.Butwhenthetwohydrogensofthemethylenebesubstitutedbyalkylgroups,thederivativeswillpossessactivities.Forexample,BarbitalandPhenobarbitalareclassicsedativehypnotic.Barbital巴比妥PhenobarbitalorLuminal苯巴比妥，魯米諾83sodiumpentothal,噴妥撒鈉，硫噴妥鈉84

Executionbylethalinjectioninvolvesthecontinuousintravenousadministrationofthreedrugs.InexecutionsconductedbytheU.S.BureauofPrisons,thefirstdrug,sodiumpentothal（噴妥撒鈉）,isabarbituratethatrendersthecondemnedpersonunconscious.Executionersthenadministerpancuroniumbromide（巴夫龍）,amusclerelaxantthatparalyzesthelungsanddiaphragmandstopsbreathing.Athirddrug,usuallypotassiumchloride（氯化鉀）,causescardiacarrestandstopstheheart.Thedrugs,administeredatlevelsthatexceedclinicaluse,shouldcausedeathwithinfiveminutes.ExecutionersflushtheIVlineswithsalinesolutionaftereachdrugtopreventthelinesfromclogging.However,blockedlinesandcollapsedveinsarecommonproblemsinthelethalinjectionprocess.Somestatesallowtheadministeringofasedativebeforeexecutiontorelaxtheinmateandmakelocatingasuitableveineasier.

TimothyMcVeighwillbeexecuted.85McVeighisexecutedat7:14June11,2001April23,1968–June11,200186April19,1995,OklahomaCitybombing87sodiumpentothal,噴妥撒鈉，硫噴妥鈉pancuroniumbromide,Pavulon,泮庫溴銨，巴夫龍KClPotassiumchloride88藥家鑫糯康89Assedativehypnotics,thederivativesofbarbituricacidarenotverysafe.Nowthederivativesofbenzodiazepine（苯并二氮卓）arewidelyuseasmoreeffectiveandmoresafesedativehypnotics,suchasDiazepamDiazepam地西泮安定90氟硝安定，F(xiàn)lunitrazepam91氟硝安定，F(xiàn)lunitrazepamFM2，十字架，“date-rapedrug”Rohypnol,氟硝西泮羅氏(HoffmanLaRoche)藥廠制造92氯胺酮，Ketamine，K仔，K粉93Ketaminecrystals94Lysergide，LSD(Lysergs?ure-di?thylamid)D-麥角酸二乙胺，麥角二乙酰胺

LSDisthemostpotentmood-andperception-alteringdrugknown:dosesassmallas30microgramscanproduceeffectslastingsixto12hours.95AlbertHofmann(艾伯特·霍夫曼)January11,1906–April29,2008“LSD,MyProblemChild”96over10stepsTamiflu(Oseltamivir)特敏福，奧司他韋，達(dá)菲shikimicacid莽草酸ShikimicacidisexractedfromspiceChinesestaraniseTamiflu(Oseltamivir)isoneofahandfulofdrugsbelievedtobeeffectiveintreatingH5N1birdflu.swineflu

H1N1972009年05月01日《廣州日報(bào)》作者:謝綺珊、趙琳琳“中午我在食堂吃的其中兩個菜就有豬肉，所以衛(wèi)生部的同志們都在吃豬肉?！毙l(wèi)生部部長陳竺支招說：“達(dá)菲的原料莽草酸主要就在八角茴香里面，我們可以把豬肉和八角茴香煮在一起，肯定是一劑良方?！?/p>

98Zanamivir,扎那米韋,樂感清Peramivir,帕拉米韋99比較化合物的堿性：1234567123100Section4AlkaloidAlkaloid:Anitrogen-containingcompound,oftenpolycyclicandgenerallyoftheplantorigin.Thetermismorelooselyappliedtoothernaturallyoccurringamines.101Lethaldose:50~70

mg(directinjection)Recently,somereportssaid,nicotinecancureseniledementia.NicotineⅠ.NicotineContentofNicotine:20~30mg/acigarette120mg/acigarSomeimportantalkaloids:102Nicotinicacid煙酸,尼克酸103Ⅱ.OpiumalkaloidsMorphine,amemberoftheclassofopiumalkaloidsconstitutesabout10%ofcrudeopium,andisanextraordinarilyeffectivepainkiller.Morphine104Poppy，罌粟105106Opium，鴉片107Codeineisanothermemberofthisfamilyandisalessaddictiveandlesspowerfulanalgesicthanmorphine.Butcodeineisaextraordinarilyeffectiveantitussive.Codeine108聯(lián)邦止咳露109CodeineCocaine110Coca,古柯111Heroin,asyntheticderivativeofmorphinenotfoundinnatureisalsoacloserelative.Theesterstructuresmakeitastrongfatsolublematerial.Heroincaneasilygetacrossbloodbrainbarrier,whichmakeitbecomestrongaddictivenarcotics.Heroin112Question:Howtosynthesizeheroinfromcodeine?113114Howtosynthesizecodeinefromheroin?115116117Wehaveknowthatmorphineisaeffectiveanalgetic.Canwesynthesizeasimplemoleculetoinsteadofmorphine?Yes,ifwecanfindthepharmacophoregroupofmorphine.Thefragmentcontainedbyredlineisthepharmacophoregroupofmorphine.Wecanaccordtothattosynthesizeanalgetic,forexample,dolantin.Dolantin,Pethidine118Dolantin,PethidineMethadone,美沙酮119鹽酸美沙酮120Ⅲ.CocaineThesynthesizeofprocaineisrelatedtococaine,canyoufindtherelationbetweenthem?localanesthetic:121Ⅳ.StrychnineStrychnineusedastoolreagentinpharmacologicalexperiment.Alsobeusedasexhilarantinathleticsports.Strychnineisapowerfulconvulsantandalethalagent.Thelethaldosageisabout30mg.士的寧，馬錢子堿，番木鱉堿122巫丹123Caffeine咖啡因Theophylline茶堿Theobromine可可堿V.Purinealkaloids124BerberineChloride鹽酸黃連素(氯化小檗堿)VI.Others125Atropine（阿托品），AtypicalMreceptorantagonist126AristoIohicAcid,馬兜鈴酸龍膽瀉肝丸毒性較大的“關(guān)木通”現(xiàn)已改為毒性較小的“木通”關(guān)木通、馬兜鈴、廣防己、青木香、天仙藤、尋骨風(fēng)、朱砂蓮等127PreparationofAromaticAmineFe/HClcanreducenitrogroupbutcannotreducecarbon-carbondoublebond.Ni,Pd,Pt1281.Sequenceo