第十章第四军医大学药学ppt课件.ppt

Generalconsideration Summary NomenclatureandStructure1 1 Nomenclature UIPACnames CommonNames1 2 Structure2 PhysicalPropertiesandSpectroscopy2 1 PhysicalProperties2 2 Spectroscopy IR 1HNMR 13CNMR MS UV3 ChemicalProperties 4 SynthesisofAldehydesandKetones5 UnsaturatedCarbonylCompounds 1 4 Addtion Diels AlderReaction Chapter10CarboxylicAcidsandSubstitutedCarboxylicAcids Carboxylgroupisusuallywritten COOHAliphaticacidshaveanalkylgroupbondedto COOHAromaticacidshaveanarylgroupFattyacidsarelong chainaliphaticacids Acarboxylicacidconsistsofthreeparts ahydroxylgroup acarbonylgroup andthe remainder 1 Nomenclature Innaming thecarboxylgrouptakespriorityoveranyoftheotherfunctionalgroupswehavediscussed 1 1 UIPACNames Monocarboxylicacids Thealiphaticcarboxylicacidsarenamedbyreplacingtheending einthenameofthealkaneby oicacidThealkanoicacidstemisnumberedbyassigningthenumber1tothecarboxycarbonSubstituentsarelabeledalongthelongestchainincorporatingtheCO2Hgroup Cycloalkaneswith COOHsubstituentsaregenerallynamedascycloalkanecarboxylicacids UnsaturatedacidsUnsaturatedacidsarenamedusingthenameofthecorrespondingalkene withthefinal ereplacedby oicacid Thecarbonchainisnumberedstartingwiththecarboxylcarbon andanumbergivesthelocationofthedoublebondThestereochemicaltermscisandtrans andZandE areusedastheyarewithotheralkenes ManysimplecarboxylicacidshavecommonnamesacceptedbyIUPAC AromaticacidsoftheformAr COOHarenamedasderivativesofbenzoicacid DicarboxylicAcids Aliphaticdicarboxylicacidsarenamedsimplybyaddingthesuffix dioicacidtothenameoftheparentalkane Aromaticdicarboxylicacidsarenamedbyaddingthewordsdicarboxylicacidto benzene ManydiacidshavecommonnamesacceptedbyIUPAC 1 1 2 CommonNames AliphaticcarboxylicacidsarenamedaccordingtotheirsourceorforsomecharacteristicpropertyTheGreekletters andsoforthareoftenaddedasaprefixtolocatesubstituentsThe positioninacarboxylicacidistheonenexttothecarboxylgroup Thenastyodorofginkgoseeds Achemicalsignalofdeadants Thetarttasteofmanyfruitsandvegetables Vinegar Ants weapon HCO2HFormicacid CH3CO2HAceticacid 1 3 Structure Thecarbonylcarbonissp2hybridizedandtrigonalplanar makingitrelativelyuncrowded Theelectronegativeoxygenatompolarizesthecarbonylgroup makingthecarbonylcarbonelectrophilic Thecarboxylgroupisplanar withoneofitscarbon oxygenbondsshorterthantheother andwithbondanglesatcarboncloseto120 sp2Hybridizationatcarbon anda carbon oxygendoublebondanalogoustothatofaldehydesandketones sp2HybridizationofthehydroxyloxygenallowsoneofitsunsharedelectronpairstobedelocalizedbyorbitaloverlapwiththesystemofthecarbonylgroupLone pairdonationfromthehydroxyloxygenmakesthecarbonylgrouplesselectrophilicthanthatofanaldehydeorketone Theelectrostaticpotentialmapofformicacidshowsthemostelectron richsitetobetheoxygenofthecarbonylgroupandthemostelectron pooronetobe asexpected theOHhydrogen 2 PhysicalPropertiesandSpectroscopy 2 1 PhysicalProperties BoilingPoints Higherboilingpointsthansimilaralcohols duetodimerformation MeltingPoints Aliphaticacidswithmorethan8carbonsaresolidsatroomtemperature Doublebonds especiallycis lowerthemeltingpoint Notethese18 Cacids Stearicacid saturated 72 COleicacid onecisdoublebond 16 CLinoleicacid twocisdoublebonds 5 C Solubility Watersolubilitydecreaseswiththelengthofthecarbonchain Upto4carbons acidismiscibleinwater Moresolubleinalcohol Alsosolubleinrelativelynonpolarsolventslikechloroformbecauseitdissolvesasadimer 2 2 SpectroscopicProperties Infrared TheO HandC Hstretchingfrequenciesoverlaptoproduceabroadabsorptioninthe3500 2500cm 1regionAstrongbandforC Ostretchingbetween1710to1760cm 1Freecarboxylgroupsabsorbat1760cm 1 butthemorecommonlyencountereddimericcarboxylgroupsabsorbinabroadbandcenteredaround1710cm 1 1HNMR Theacidicprotonofacarboxylicacidproducesasignalthatisusuallybroadandappearsintheregion 10 13Thisprotonisexchangeablewithdeuteriumofasolventcontainingthe ODlinkage suchasD2OProtonsofthe carbonpositioncomeintoresonanceinthesameregionasdothoseofaldehydesandketones 2 2 5 13CNMR Thecarbonylgroupofacarboxylicacidderivativegenerallyappearsintheregionbetween160and185ppm MassSpectrometry UVSpectroscopy Saturatedcarboxylicacidsabsorbveryweaklyaround200 215nm IfC CisconjugatedwithC O molarabsorptivity 10 000at200nm Anadditionalconjugateddoublebondincreasestheabsorptionwavelengthto250nm 3 ChemicalProperties sp2HybridizationofthehydroxyloxygenallowsoneofitsunsharedelectronpairstobedelocalizedbyorbitaloverlapwiththesystemofthecarbonylgroupLone pairdonationfromthehydroxyloxygenmakesthecarbonylgrouplesselectrophilicthanthatofanaldehydeorketone Generalconsideration 3 1 Acidity Carboxylicacidsarethemostacidicclassofcompoundsthatcontainonlycarbon hydrogen andoxygen ResonanceStabilization AcidityComparedtoAlcohols Carboxylicacidsarebetterprotondonorsthanarealcohols ThepKaofethanolis 16 comparedto 5foraceticacid Inanalkoxideion thenegativechargeislocalizedonoxygenwhileinacarboxylateionthenegativechargeisdelocalizedovertwoequivalentoxygenatoms givingresonancestabilization AcidityConstantandpKa CarboxylicacidstransferaprotontowatertogiveH3O andcarboxylateanions RCO2 butH3O isamuchstrongeracidTheacidityconstant Ka isabout10 5foratypicalcarboxylicacid pKa 5 SubstituentEffects Anelectronegativegroupwilldrivetheionizationequilibriumtowarddissociation increasingacidity Anelectron donatinggroupdestabilizesthecarboxylateanionanddecreasesacidity Alkylgroupshavelittleeffect TheionizationconstantsofallacidsthathavethegeneralformulaCnH2n 1CO2Hareverysimilartooneanotherandequalapproximately10 5 pKa 5 Anelectronegativesubstituent particularlyifitisattachedtothe carbon increasestheacidityofacarboxylicacid Monohaloaceticacidsisabout100timesmoreacidicthanaceticacid Multiplehalogensubstitutionincreasestheacidityevenmore trichloroaceticacidis7000timesmoreacidicthanaceticacid SubstituentEffectsonAcidity SubstituentEffectsonAcidity Electronegativesubstituentspromoteformationofthecarboxylateion ExamplesofInductiveEffectsonAcidity Fluoroacetic chloroacetic bromoacetic andiodoaceticacidsarestrongeracidsthanaceticacidMultipleelectronegativesubstituentshavesynergisticeffectsonacidity Inductiveeffectsdependontheelectronegativityofthesubstituentandthenumberofbondsbetweenitandtheaffectedsite Asthenumberofbondsincreases theinductiveeffectdecreases AcidityofSubstitutedBenzoicAcids Benzoicaciditselfisasomewhatstrongeracidthanaceticacid Carbonbecomesmoreelectron withdrawingasitsscharacterincreases Thelargesteffectsareobservedwhenstronglyelectron withdrawingsubstituentsareorthotothecarboxylgroup Substituentatmetaposition Aninductiveeffect Substituentatparaposition Anresonanceeffectandinductiveeffect andresonanceeffectoutweighstheinductiveeffectSubstituentatorthoposition Nearlyallorthosubstituentsexertaneffectofthesamekindacid strengtheningwhethertheyareelectron withdrawingorelectron releasing andtheeffectisunusuallylarge SubstituentEffectsinSubstitutedBenzoicAcids AromaticSubstituentEffects Anelectron withdrawinggroup NO2 increasesaciditybystabilizingthecarboxylateanionAnelectron donating activating group OCH3 decreasesaciditybydestabilizingthecarboxylateanion Ifwewanttoknowtheeffectofacertainsubstituentonelectrophilicreactivity wecansimplyfindtheacidityofthecorrespondingbenzoicacid SubstituentEffectsinSubstitutedBenzoicAcids Diacidshavetwodissociationconstants Ka1isforthefirstdissociation andKa2isfortheseconddissociation togiveadianion Thesecondcarboxylgroupismuchlessacidicthanthefirst Ka2 Ka1 becauseextraenergyisrequiredtocreateasecondnegativechargeclosetoanother mutuallyrepulsive negativecharge Thisrepulsiveeffectdecreasesasthechaingetslonger FieldEffects TheElectrostaticInterpretation FormationofSalts InthepresenceofbasessuchasNaOH Na2CO3andNaHCO3 carboxylicacidsareneutralizedrapidlyandquantitatively Addingastrongacid likeHCl regeneratesthecarboxylicacid PropertiesofAcidSalts Usuallysolidswithnoodor CarboxylatesaltsofNa K Li andNH4 aresolubleinwater Soapisthesolublesodiumsaltofalongchainfattyacid SaltscanbeformedbythereactionofanacidwithNaHCO3 releasingCO2 PurifyinganAcid 3 2 SubstitutionattheCarboxyCarbon 3 2 1 FischerEsterification Thereactionofacarboxylicacidwithanalcoholinthepresenceofanacidcatalysttoformanester EmilFischer 1852 1919 wasaGermanChemistandwontheNobelPrizeinChemistryin1902 HediscoveredtheFischeresterification anddevelopedtheFischerprojection asymbolicwayofdrawingasymmetriccarbonatoms Acid catalyzedesterificationisreversibleAlargeexcessofalcoholRemovalofwater azeotropicdistillationandaDean Starktrap In1938 IrvingRobertsandHaroldC UreyofColumbiaUniversityconfirmedthattheC Obondofthealcoholispreservedduringesterification andtheoxygenthatislostasawatermoleculemustcomefromthecarboxylicacid HaroldClaytonUrey 1893 1981 wasanAmericanphysicalchemistwhosepioneeringworkonisotopesearnedhimtheNobelPrizeinChemistryin1934 Heplayedasignificantroleinthedevelopmentoftheatombomb HaroldUrey MechanismofFischeresterification Thepresenceofbulkygroupsnearthesiteofreaction whetherinthealcoholorintheacid slowsdownesterification aswellasitsreverse hydrolysis Reactivityinesterification CH3OH 1 2 3 HCOOH CH3COOH RCH2COOH R2CHCOOH R3CCOOHThissterichindrancecanbesomarkedthatspecialmethodsarerequiredtoprepareestersoftertiaryalcoholsorestersofacidslike2 4 6 trimethylbenzoicacid mesitoicacid Synthesisoftert butylesters Mechanism Esterificationof2 4 6 trimethylbezoicacid Thethreeelementsofthechemistryofcarboxylicacidderivatives Theseelementsare1 Activationofthecarbonylgroupbyprotonationofthecarbonyloxygen2 Nucleophilicadditiontotheprotonatedcarbonyltoformatetrahedralintermediate3 EliminationfromthetetrahedralintermediatetorestorethecarbonylgroupThissequenceisfundamentaltothecarbonyl groupchemistryofcarboxylicacids acylchlorides anhydrides esters andamides 3 2 2 FormationofAcylHalides AcidAnhydridesandAmides Thefunctionalgroupofanacylhalideisacarbonylgroupbondedtoahalogenatom Theconversionofcarboxylicacidsintoacylhalidesemploysthesamereagentsusedinthesynthesisofhaloalkanesfromalcohols GeneralReactions Mechanism Anacidanhydride two