化学chapter-18-Heterocyclic-compounds杂环化合物课件

2023/7/271Chapter18

Heterocyclic

compounds1CHAPTER172023/7/271Chapter18Heterocyc2023/7/272Heterocycliccompounds,orheterocycles,arecycliccompoundsin

whichoneormoreoftheatomoftheringareheteroatoms.Avarietyofatomscanbeincorporatedintoringstructures.Inthischapter,wewillonlyconsiderthehetroatomsN,O,S.Almostallthecompoundsweknowasdrugs,mostvitamins,andmanyothernaturalproductsareheterocycles.2CHAPTER172023/7/272Heterocycliccompoun2023/7/273poundsnaturalproductisacompoundsynthesized

byaplant

orananimal.Alkaloidsarenaturalproductscontainingoneormorenitrogenheteroatomsthatarefoundintheleaves,bark,roots,orseedsoftheplants.A3CHAPTER172023/7/273poundsnaturalprodu2023/7/274Otherheterocyclesincludevalium,asynthetictranquilizer,andserotonin,aneurotransmitter.4CHAPTER172023/7/274Otherheterocycles42023/7/275Saturatedheterocycles5CHAPTER172023/7/275Saturatedheterocycl2023/7/276Unsaturatedfive-membered-ringheterocyclesPyrrole,furan,andthiophenearefive-membered-ring

heterocycles.Pyrrole,furan,andthiophenearearomaticbecausetheyarecyclicandplanar,everycarbonintheringhasaporbital,andtheπcloudcontainsthreepairsofπelectrons.6CHAPTER172023/7/276Unsaturatedfive-me2023/7/277TheseelectronsarepartoftheπcloudTheseelectronsareinasp2orbital7CHAPTER172023/7/277Theseelectronsare2023/7/278Pyrroleisanextremelyweakbase.Thiophene,withtheleastelectronegativeheteroatom,hasthe

greatest

resonanceenergyWhilefuranhasthesmallestresonanceenergy.Relativeresonanceenergiesofsomearomaticcompounds8CHAPTER172023/7/278Pyrroleisanextrem2023/7/279Dipolemomentoffive-member-ringheterocycles9CHAPTER172023/7/279Dipolemomentoffiv2023/7/2710Electrophilicaromaticsubstitutionmorereactivethanbenzene,Substitutionoccursprefer-entiallyatC-2,ifbothpositionsadjacenttothe

hetero-atomareoccupied,substitutionwilltakeplaceatC-3.

Forexample10CHAPTER172023/7/2710Electrophilicaroma2023/7/2711Furanisnotasreactiveaspyrroleinelectrophilicsubstitution.MechanismRelativereactivitytowardelectrophilicsubstitution11CHAPTER172023/7/2711Furanisnotasrea2023/7/2712

Thiopheneislessreactivethanfuran,becausesulfur’spelectronsarein3porbital,whichoverlapslesseffectivelythanthe2porbitalofNitrogen

oroxygenwiththe2porbitalofcarbon.

Theoxygenoffuranismore

electronegativethanthenitrogenofpyrrole,sotheoxgenisnotaseffectiveasnitrogenindonatingelectronsintothering.12CHAPTER172023/7/2712Thiopheneisles2023/7/2713TherelativereactivitiesofthemarereflectedintheLewisacidrequiredtocatalyzeaFriedel-CraftsAcylationreaction.13CHAPTER172023/7/2713Therelativereacti2023/7/2714Ring-openreactionUsually,pyrroledoesnotundergothisreaction,butitisunstableinstrongacidicsolutionsbecauseofpolymerization.Furaniseasilyhydrolyzedinacidicaqueoussolution.ThiophenecanbereducedtoalkaneunderNiCatalystbyH2.14CHAPTER172023/7/2714Ring-openreaction2023/7/2715Indole,benzofuran,andbenzothiopheneElectrophilicsubstitution:indoleundergoeselectrophilicsubstitutionprimarilyatC-3,benzofuranprimarilyatC-2,andBenzothiopheneaboutequallywellatC-2andC-3.Forexample,15CHAPTER172023/7/2715Indole,benzofuran,2023/7/2716PyridineWhenoneofthecarbonsofabenzeneringisreplacedbyanitrogen,theresultingcompoundiscalledpyridine.Unsaturatedsix-membered-ringheterocycles16CHAPTER172023/7/2716PyridineUnsaturated2023/7/2717Pyridineisatertiaryamineandundergoesreactionscharacteristicoftertiary.forexample,pyridineundergoesSN2reactionswithalkylhalides.anditreactionwithH2O2toformanN-oxide.17CHAPTER172023/7/2717Pyridineisaterti2023/7/2718Becauseitisaromatic,pyridineundergoeselectrophilicsubstitution.Pyridine’selectron-withdrawingnitrogencausestheringcarbonstohavesignificantlylesselectrondensitythantheringcarbonsofbenzene.Relativereactivitytowardelectrophilicsubstitution18CHAPTER172023/7/2718Becauseitisaroma2023/7/2719Pyridineundergoeselectrophilicsubstitutionreactionsonlyatvigorousconditions,andoftenwithlowyield.ifthenitrogenbecomeprotonatedunderthereactionconditions,thereactivityisfurtherdecreased.ItDoesnotundergoFreidel-craftsreaction.19CHAPTER172023/7/2719Pyridineundergoes2023/7/2720WhyreactionstakeplaceatC-3?20CHAPTER172023/7/272020CHAPTER172023/7/2721Pyridineismorereactivitytowardnucleophilicaromaticsubstitutionthanbenzene.MechanismfornucleophilicaromaticsubstitutionThereactiontakesplaceatC-2andC-421CHAPTER172023/7/2721Pyridineismorere2023/7/2722IftheleavinggroupsatC-2andC-4aredifferent,theincomingnuclophilewillpreferentiallysubstitutefortheweakbase(thebetterleavinggroup).Forexample22CHAPTER172023/7/2722Iftheleavinggrou2023/7/2723Substitutedpyridinesundergomanyoftheside-chainreactionsthatsubstitutedbenzenesundergo.When2-or4-aminopyridineisdiazotized,α-pyridoneorγ-pyridoneisformed23CHAPTER172023/7/2723Substitutedpyridin2023/7/2724Theelectron-withdrawingnitrogencausestheα-Hydrogensofalkylgroupsattachedtothe2-and4-positionsofthepyridineringtohaveaboutthesameacidityastheα-hydrogensofketones.24CHAPTER172023/7/2724Theelectron-withdr2023/7/2725QuinollineandisoquinolineQuinolineandisoquinolineareknownasbenzopyridines,becausetheyhavebothbenzeneandpyridinerings.TheyArearomaticcompounds25CHAPTER172023/7/2725Quinollineandisoqpreparation1.Skraupsynthesis(anilineandglycerol)26CHAPTER17preparation1.Skraupsynthesis(27CHAPTER1727CHAPTER1728CHAPTER1728CHAPTER172.Friedländersynthesis(ortho-aminoaromaticaldehyde/ketoneandcarbonylcompoundswithα-H).29CHAPTER172.Friedländersynthesis29CHAPTSynthesisofisoquinolinanditsderivativesBischler-Napieralskisynthesisacylationofβ-phenylethylamine,dehydration,dehydrogenatiokn.30CHAPTER17Synthesisofisoquinolinandi2023/7/2731Electrophilicaromaticsubstitutiononthebenzenering,substitutiontakesplaceprimaryatC-5andC-8.31CHAPTER172023/7/2731ElectrophilicaromaElectrophilicsubstitusiontakeplaceatC-5andC-8.Chemicalproperties32CHAPTER17Electrophilicsubstitusiontak2023/7/2733Nucelophilcaromaticsubstitutiononthepyridinering,QuinolinundergoesnucleophilicsubstitutionatC-2andC-4,whileisoquinolineundergoesnucleophilicsubstitutiononlyatC-1.33CHAPTER172023/7/2733NucelophilcaromatiTheelectron-withdrawingnitrogencausestheα-Hydrogensofalkylgroupsattachedtothe2-and4-positionsofthequinolinor1-positionofisoquinolintohaveaboutthesameacidityastheα-hydrogensofketones.34CHAPTER17Theelectron-withdrawingnitroOxidationandreductionOxidationtakesplaceatphenylringReductiontakesplaceatpyridinering35CHAPTER17Oxidationandreduction35CHAPT2023/7/2736imidazoleBiologicallyimportantheterocycles36CHAPTER172023/7/2736imidazoleBiological2023/7/2737PurineandpyrimidineDNAandRNAcontainsubstitutedpurinesandpyrimidine.Unsubstitutedpurineandpyrimidinearenotfoundinnature.Pyrimidineisamuchweakerbasethan

pyridine,the

conjugatedacidisastrongeracid,PKa=1,purineconsistsofapyrimidineringfusedtoanimidazolering,soithasthepropertiesofbothring

systems.37CHAPTER172023/7/2737Purineandpyrimidi2023/7/2738Theelectron-donatingimidazoleringmakestheprotonatedpyrimidinering(Pka=2.5)lessacidicthan

unsubstitutedprotonatedpyrimidine.Theelectron-withdrawingpyrimidineringmakes

thehydrogenonN-9moreacidicthanthe

correspondingN-1hydrogenofimidazole.38CHAPTER172023/7/2738Theelectron-donati2023/7/2739Porphyrine39CHAPTER172