AminesCompoundscontainingNitrogenatom本章內容；1、硝基化合物(nitrocompounds)2、胺(amines)3、季銨鹽和季銨堿(Quaternary

Saltsand

QuaternaryAmmoniumHydroxides)4、重氮化合物與偶氮化合物

(diazoandazocompounds)第一節、硝基化合物硝基化合物(nitrocompounds)是指烴分子中的氫原子被硝基(－NO2)nitro-group取代后得到的化合物，一元硝基化合物常用RNO2或ArNO2表示。ExampleNitrocompoundsNitriteester硝基化合物亞硝酸酯Structure127O122pm122pm硝基中，氮原子為sp2雜化氮原子上未雜化的p軌道和兩個氧原子上的p軌道互相重疊，形成包括三個原子在內三中心四電子的大π鍵分子軌道：Nomenclature與鹵烴相類似，以烴為母體，硝基作為取代基。例如：

nitroethane

2-nitropropane

4-nitrotoluene2,4,6-trinitrotoluene

Chenmicaireaction1.有關硝基對α-H影響的反應(1)酸性Why?Goodnucleophilicreagent硝基式假酸式酸性和互變異構具有α氫的硝基化合物與強堿作用生成鹽：含α氫的1°和2°脂肪族硝基化合物能逐漸溶于強堿的水溶液中并形成鹽，表現出明顯的酸性。一般認為這是由于這些硝基化合物中存在著下列互變異構現象：(2)縮合反應2.硝基對鄰、對位取代基活性的影響

加成消除機理使甲基的氫易離去3.硝基的還原在堿性介質中發生雙分子還原在中性介質中生成苯基羥胺選擇性還原Impossibletopredictwhichnitrogroupwillbereduced

AminesAminesareusedin…殺蟲劑Pesticide染料Dye制藥Manufacturesdrugs聚合物PolymerAminesare…氨的衍生物(NH3).它既是堿又是酸第二節、胺類SomeExamplescocaine

3°aminestreucturecocainecocaine

plantcocaine

flower

苯丙胺類興奮劑均具有中樞神經系統興奮作用，但不同藥物的作用各有側重amphetamine

NicotineCaffeineProcaine胺是氨的衍生物ammoniaamine

derivatives1o2o3oPrimaryamineSecondaryamineTertiaryaminequaternary

salt1.Classification:可為aliphatic,aromatic,andhetero-cyclicamines:aliphaticamines:氮直接連接在脂基上aromaticamines:氮直接連接在芳基上heterocyclicamines:氮在環中2.Nomenclaturemethylamine

ethylamine

cyclohexylaminetert-butylamine1).Primaryamines(RNH2)arenamedbyaddingtheword“amine”tothenameoftheRgroup.PrimaryaminescanbenamedinIUPACsystemintwoways2).analogoustoalcohols:replace-eendingby-amineCH3CH2NH2ethanamineNH2cyclohexanamineCH3CHCH2CH2CH3NH22-pentanamine3)NomenclatureofPrimaryArylamines(ArNH2)NameasderivativesofanilineNH2只有當氨基直接連接在芳環上才是芳香胺

Examples:someprimaryarylamines(ArNH2:onecarbondirectlyattachedtoN)p-fluoroaniline5-bromo-2-ethylanilineNH2FNH2BrCH2CH3AminogroupsassubstituentsaminogroupsrankbelowOHgroupsandhigheroxidationstatesofcarboninsuchcasesnametheaminogroupasasubstituentp-aminobenzaldehydeNH2HCOHOCH2CH2NH22-aminoethanoldimethylamine

triethylamine

dicyclohexylamineSymmetricalsecondary(R2NH)andtertiaryamines(R3N)arenamedbyadding“di-”or“tri-”asprefixestothenameoftheRgroup.N-methylethylamine

N-methyldiethylamine

N,N-dimethylethylamineUnsymmetricalsecondary(RR’NH)andtertiaryamines(RR’R”N)arenamedasN-substitutedprimaryamines.ThelargestRgroupdeterminesthenameoftheamine.N-ethyl-N-methylpropylamineExamplesCH3NHCH2CH3N-methylethylamineNHCH2CH3NO2Cl4-chloro-N-ethyl-3-nitroanilineCH3NCH3N,N-dimethylcycloheptylamineAmmoniumSaltsAnitrogenwithfoursubstituentsispositively

chargedandisnamedasaderivativeof

ammoniumion(NH4+).CH3NH3+Cl–methylammonium

chlorideNCH3HCH2CH3+CF3CO2–N-ethyl-N-methylcyclopentylammonium

trifluoroacetateAmmoniumSaltsWhenallfouratomsattachedtoNarecarbon,

theioniscalledaquaternaryammoniumionand

saltsthatcontainitarecalledquaternary

ammoniumsalts.+CH2NCH3CH3CH3I–benzyltrimethylammoniumiodide3.Structure147pm112106Alkylamines甲胺的結構

胺具有棱錐形的結構.Theaminestructureandtheammoniaaresimilar.

nitrogenatomissp3hybridization,

theamineasthetetrahedralstructure,nitrogenatomseemstobeaschiralatoms.simpleamineenantiomersresolutiondidnotsucceed.氨、甲胺和三甲胺的結構如下：Aromaticaminesarealsosp3hybridization，nitrogenatombondedwiththecarbonatomsofsp2

hybridcarbon，alsomakesthenitrogenatomasthecenterofthetetrahedron,thealiphaticaminesareintheflatshape，porbitalofthenitrogenconjugatedwiththebenzenering.Structureofaniline

INVERSIONOFSMALLAMINESIffastinversionoccurs,apyrimidalnitrogenwillnotbeanactivestereocenter.RACEMICMIXTUREOFENANTIOMERS手性季銨鹽正離子，可以被拆開成對映體。activestereocenterBICYCLICAMINESAREUSUALLYRIGID

CH3HTheringscannotinvert.******Thenitrogenisrigidlyheldinthebicyclicringsandcannotinvert.(1)BasicityofAmines

Inaqueousalkalinesequenceofaliphaticissecondaryamine>primaryamine>tertiaryamine,(CH3)2NH>CH3NH2>(CH3)3N>NH3measuredinthegasphase,aminebasicsequenceisatertiaryamine>secondaryamines>primaryamine.

4.ChemicalPropertiesIfweconsideronlythesolvationeffectofdifferentamine,thebasicordershouldbeprimaryamine>secondaryamine>tertiaryamine.

Therefore,theoverallevaluationaboveinfluencealkalinitythreekindoffactors(electroniceffect,solvationeffectandspatialeffect),intheaqueoussolution,thesecondaryaminealkalinityarestrongest,butprimaryamineandtertiaryaminearenext.

C6H5NH2(C6H5)2NH(C6H5)3NKb3.8x10-106x10-14~10-19Thealkalinityofaromaticamineismuchweakerthantheammonia,thisisbecauseintheanilineinthenitrogenwithpairofunsharedelectronhastheconjugationwiththebenzenering,reducedonthenitrogenatomelectrondensity,causesitsalkalinitytoweakengreatly.

PhNH2>Ph2NH>Ph3NEffectofsubstituents①

Forthevastmajorityofsubstituents,whetheritiselectron-donatinggroupsorelectron-withdrawinggroups,inortho-substituentsaregenerallyreducedtoalkaline(inthetable,excepttoOH).PhNH2>>>pKa4.624.392.70-0.3②

electron-donatinggroupsenhancedthealkaline,electron-withdrawinggroupstoweaken;在對位比在間位更為明顯。③Forthetwoeffectsofonegroups,itsimpactdependsontwokindofeffectthedirectionandrelativestrength.

Speakingofthechlorine,itisintheaminothepara-position,alsohasattractselectronictheinductiveeffectandfortheelectronicconjunctiveeffect,butitsconjunctiveeffectmustweaklyintheinductiveeffect,thereforethealkalinitywillbeweaken,Buthalogeninthemeta-position,onlytheelectronwithdrawinginductiveeffectatwork,sothealkalinitydeclinemore.

PhNH2pKa4.003.48

芳香胺的堿性比氨和脂胺弱得多，這是因為氮上未共用電子對與苯環有共軛作用，分散了氮上的這一對電子，使其堿性大大減弱。在芳胺中，氮上的氫原子若被烷基取代，會使堿性增強。如：PhN(CH3)2>PhNHCH3>PhNH2芳胺和脂胺的堿性比較芳脂胺的堿性大于芳胺。季銨堿因在水中可完全電離,因此是強堿,其堿性與氫氧化鉀相當。Butthemethoddoesn'tworkwellinpractice.

Usuallygivesamixtureofprimary,secondary,

andtertiaryamines,plusthequaternarysalt.

AlkylationofAmmonia（2）AlkylationExampleAsoctylamineisformed,itcompeteswithammoniafortheremaining1-bromooctane.Reactionofoctylaminewith1-bromooctanegivesN,N-dioctylamine.CH3(CH2)6CH2BrNH3CH3(CH2)6CH2NH2(45%)+CH3(CH2)6CH2NHCH2(CH2)6CH3(43%)

（3）Acylation

Conversionofaminesintosubstituted

amidesammoniareactswithacidchloridesandsulfonylchlorides

?；酋；痯rimaryandsecondaryaminescanalsoreactwithacidchloridestoformsubstitutedamides.Buttertiaryaminesfailtoyieldamides.

Application①.Analysisofamines.HinsbergtestApplication②.Protecttheaminogroupinsynthesis③.SynthesisofSulfanilamide:Thesulfadrugs（4）ReactionsofAmineswithnitrousacid①.Diazotizationreaction：Reactionsof

PrimaryArylamines

withNitrousAcidStructureofarenediazoniumsaltsReactionsMechanismofPrimaryArylamineswithNitrousAcidReactionsofPrimaryAliphaticAmineswithNitrousAcid定量放出氮氣測定－NH2的量混合物無制備價值Ring-expansionreaction；可用于制備五至九元的環酮。例如：②．Reactionsof

SecondaryAmines

withNitrousAcid

obtain

N-nitrosoamines.例如：SolidoryellowcompoundactsasidentificationN-Nitrosoamines:Verypowerfulcarcinogens,maybepresentinmanyfoods,especiallyincookedmeats③.Reactionsof

TertiaryAmines

with

NitrousAcidUnstableproductColorproductcanidentifyAraminesArylamines;

（5）ElectrophilicAromatic

Substitution

inArylamines①.Nitrationoccursreadilywithoutnecessityofprotecting

aminogroup,butdifficulttolimitittomonohalogenation硫酸氨基是間位定位基乙酰氨基是鄰對位定位基②.HalogenationofArylamines反應定量完成，可用作定性、定量分析。③.Friedel-CraftsReactionsTheaminogroupofanarylaminemustbeprotectedasanamidewhencarryingoutaFriedel-Craftsreaction.NHCCH3OCH2CH3CH3CClOAlCl3(57%)NHCCH3OCCH3OCH2CH3④.Sulfonationreaction

rearrangment磺胺類藥物母體磺化氯磺化

Section3Quaternary

Saltsand

QuaternaryAmmoniumHydroxides

Phase-TransferCatalystsPhase-TransferCatalysisQuaternaryammoniumsaltsarephase-transfer

catalysts.Theyaresolubleinnonpolarsolvents.NH3CCH2CH2CH2CH2CH2CH2CH2CH3CH2CH2CH2CH2CH2CH2CH2CH3CH2CH2CH2CH2CH2CH2CH2CH3+Cl–Methyltrioctylammonium

chloridePhase-TransferCatalysisCl–BenzyltriethylammoniumchlorideNCH2CH3CH2CH3CH2CH3+ExampleTheSN2reactionofsodiumcyanidewithbutyl

bromideoccursmuchfasterwhenbenzyl-

triethylammoniumchlorideispresentthanwhen

itisnot.CH3CH2CH2CH2Br+NaCNCH3CH2CH2CH2CN+NaBrBenzyltriethylammoniumchloride

The

HofmannElimination(positionofquaternaryammoniumhydroxide)Hofmann,AugustWilhelm

Born:Giessen(Germany),1818

Died:Berlin(Germany),18921.TheaminetreatedwithexcessmethyliodidetoconvertittothequaternaryammoniumiodideHofmannexclusivemethylation2.Converttheiodidetohydroxidebysilveroxide3.Heatingthedryquaternaryammoniumhydroxide

MechanismRegioselectivityheatEliminationoccursinthedirectionthatgives

theless-substituteddoublebond.Thisiscalled

theHofmannrule.N(CH3)3+HO–CH3CHCH2CH3H2CCHCH2CH3CH3CHCHCH3+(95%)(5%)Regioselectivity

N(CH3)3+HHHHCH3CH2CHCHHCH3CH2largestgroupisbetweentwoHatomsmajorproductTheHofmannElimination

aquaternaryammoniumhydroxideisthereactantandanalkeneistheproductisan

antielimination，theleavinggroupisatrialkylamine，theregioselectivityis

oppositetotheZaitsevrule.

Example

ExampleSection4、DiazoandAzocompounds1.DiazoCompounds制備；芳香族伯胺與亞硝酸在低溫下反應，生成重氮鹽。TransformationsofArylDiazoniumSaltsArNN+ArHArOHArIArFArBrArClArCNExample①2.H2O,heat(CH3)2CHNH21.NaNO2,H2SO4H2O,0-5°C(CH3)2CHOH(73%)Example②2.KI,roomtemp.1.NaNO2,HClH2O,0-5°C(72-83%)NH2BrIBrExample③(68%)NH2CCH2CH3O2.HBF41.NaNO2,HCl,H2O,0-5°C3.heatFCCH2CH3OSchiemannreactionExample④(68-71%)NH2NO22.CuCl,heat1.NaNO2,HCl,H2O,0-5°CClNO2Sandmeyer

reactionsTraugottSandmeyer(1854-1922),wasborninWettingen,Switzerland,andreceivedhisPh.D.attheUniversityofHeidelberg.HespenthisprofessionalcareerdoingpharmaceuticalresearchattheGeigyCompany,Switzerland.Example⑤(89-95%)2.CuBr,heat1.NaNO2,HBr,H2O,0-10°CNH2ClBrClSandmeyer

reactionsSynthesizem-BromochlorobenzenenitrationchlorinationreductiondiazotizationSandmeyerreactionusethediazotizationandSandmeyerreactions.Example⑥(64-70%)2.CuCN,heat1.NaNO2,HCl,H2O,0°CNH2CH3CNCH3SandmeyerreactionExample⑦(70-75%)NaNO2,H2SO4,H3PO2NH2CH3CH3reductivedeaminationNH2BrBrBrExample⑧(74-77%)NaNO2,H2SO4,

H2O,CH3CH2OHNH2Br2H2O(100%)BrBrBrAnothervalueusageofDiazoniumSalts2.AzoCompound

DiazoniumsaltsreactwithstronglyactivatedaromaticcompoundsbyelectrophilicaromaticsubstitutionandgiveAzocompoundArNN+Ar'H+ArNNAr'anazocompoundAr'mustbearastronglyelectron-releasinggroup

suchasOH,OR,orNR2.ExampleOH+C6H5NN+OHNNC6H5Cl–

1.GabrielSynthesis

2.PreparationofAminesbyReduction

3.ReductiveAmination

4.LeuckartReaction

5.MannichReactionPreparationofAmines1.GabrielSynthesis

Gabrielsynthesisisthepreparationofpureprimaryaminemethod,firstinthestrongalkalineconditions,thephthalimidetransformintophthalimideanion,theanionandalkylhalidealkylation,andthenhydrolyzedtoobtainapureprimary

amine.ExampleOON?

??

?–K++C6H5CH2ClOONCH2C6H5?

?DMF(74%)GabrielSynthesisphthalimideanion+C6H5CH2NH2OONCH2C6H5?

?H2NNH2(97%)OONHNHPreparationofprimaryamineN-取代物在堿或酸中水解速度較慢、產率較低，現多用肼代替酸或堿進行肼解。thealcoholsulfonylacidesterisagoodreagent,

GabrielreactionisSN2nucleophilicsubstitutionreaction,iftheleavinggroupisconnectedwiththecarbonatomischiralcarbonatoms,theconfigurationwillbetransformed.SiegmundGabriel

(1851-1924)wasborninBerlin,Germany,andreceivedhisPh.D.in1874attheUniversityofBerlin,workingwith

AugustvonHofmann.Afterfurther

workwith

RobertBunsen,hebecameProfessorofChemistryattheUniversityofBerlin

SynthesisofAminesviaAzidesSN2reaction,followedbyreduct