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Chapter 18- Ethers and Epoxides; Thiols and Sulfides
Ethers and Their Relatives
• Anetherhastwoorganicgroups(alkyl,aryl,orvinyl)bondedtothesameoxygenatom,R–O–Rʹ
• Diethyletherisusedindustriallyasasolvent• Tetrahydrofuran(THF)isasolventthatisacyclicether
• Thiols(R–S–H)andsulfides(R–S–Rʹ)aresulfur(foroxygen)analogsofalcoholsandethers
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Why do I care, Dr. P?
• TofinishcoveringfuncKonalgroupswithC-OandC-Ssinglebonds
• FocusonethersandlookatthiolsandsulfidesbeforegoingontoC=O
Nomenclature
1) SimpleethersarenamedbyidenKfyingthetwoorganicsubsKtuentsandaddingthewordether
2) IfotherfuncKonalgroupsarepresent,theetherpartisconsideredanalkoxysubsKtuent
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Electronic structure
• R–O–R~tetrahedralbondangle(112°indimethylether)
• Oxygenissp3-hybridized• Oxygenatomgivesethersaslightdipolemoment
Synthesis of Ethers
• Diethyletherpreparedindustriallybysulfuricacid–catalyzeddehydraKonofethanol–alsowithotherprimaryalcohols
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The Williamson Ether Synthesis
• ReacKonofmetalalkoxidesandprimaryalkylhalidesandtosylates
• BestmethodforthepreparaKonofethers• AlkoxidespreparedbyreacKonofanalcoholwithastrongbasesuchassodiumhydride,NaH
Silver Oxide-Catalyzed Ether Formation
• ReacKonofalcoholswithAg2Odirectlywithalkylhalideformsetherinonestep
• GlucosereactswithexcessiodomethaneinthepresenceofAg2Otogenerateapentaetherin85%yield
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Alkoxymercuration of Alkenes
• Reactalkenewithanalcoholandmercuricacetateortrifluoroacetate
• DemercuraKonwithNaBH4yieldsanether• OverallMarkovnikovaddiKon
Learning check
• Howwouldyoupreparethefollowingether?
O
O CF3CO2H
O
CH3 1. NaNH2, NH32. H2O
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Reactions of Ethers: Acidic Cleavage
• EthersaregenerallyunreacKve• Strongacidwillcleaveanetheratelevatedtemperature• HI,HBrproduceanalkylhalidefromlesshinderedcomponent
bySN2(terKaryethersundergoSN1)
Reactions of Ethers: Claisen Rearrangement
• Specifictoallylarylethers,ArOCH2CH=CH2• HeaKngto200–250°Cleadstoano-allylphenol• ResultisalkylaKonofthephenolinanorthoposiKon
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Claisen Rearrangement Mechanism
• Concertedpericyclic6-electron,6-memberedringtransiKonstate
• Mechanismconsistentwith14Clabeling
Learning check
• Predicttheproduct(s)ofthefollowingreacKon:
O
O CF3CO2H
O
CH3 1. NaNH2, NH32. H2O
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Cyclic Ethers: Epoxides
• Cyclicethersbehavelikeacyclicethers,exceptifringis3-membered
• Dioxaneandtetrahydrofuranareusedassolvents
Epoxides (Oxiranes)
• Threememberedringetheriscalledanoxirane(root“ir”from“tri”for3-membered;prefix“ox”foroxygen;“ane”forsaturated)
• Alsocalledepoxides• Ethyleneoxide(oxirane;1,2-epoxyethane)isindustrially
importantasanintermediate• PreparedbyreacKonofethylenewithoxygenat300°Cand
silveroxidecatalyst
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Preparation of Epoxides Using a Peroxyacid
• Treatanalkenewithaperoxyacid
Epoxides from Halohydrins
• AddiKonofHO-Xtoanalkenegivesahalohydrin• Treatmentofahalohydrinwithbasegivesanepoxide
• IntramolecularWilliamsonethersynthesis
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Reactions of Epoxides: Ring-Opening
• Wateraddstoepoxideswithdiluteacidatroomtemperature• Productisa1,2-diol(onadjacentC’s:vicinal)• Mechanism:acidprotonatesoxygenandwateraddsto
oppositeside(transaddi1on)
Halohydrins from Epoxides
• AnhydrousHF,HBr,HCl,orHIcombineswithanepoxide
• Givestransproduct
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Regiochemistry of Acid-Catalyzed Opening of Epoxides
• NucleophilepreferablyaddstolesshinderedsiteifprimaryandsecondaryC’s
• AlsoatterKarybecauseofcarbocaKoncharacter
Regiochemistry of Acid-Catalyzed Opening of Epoxides
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Base-Catalyzed Epoxide Opening
• Strainofthethree-memberedringisrelievedonring-opening
• Hydroxidecleavesepoxidesatelevatedtemperaturestogivetrans1,2-diols
Addition of Grignards to Ethylene Oxide
• Adds–CH2CH2OHtotheGrignardreagent’shydrocarbonchain
• Acyclicandotherlargerringethersdonotreact
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Learning check
• PredictthemajorproductofthefollowingreacKonbelow:
O
O CF3CO2H
O
CH3 1. NaNH2, NH32. H2O
Crown Ethers
• LargeringsconsisKngrepeaKng(-OCH2CH2-)orsimilarunits• Namedasx-crown-y
• xisthetotalnumberofatomsinthering• yisthenumberofoxygenatoms• 18-crown-6ether:18-memberedringcontaining6oxygenatoms
• CentralcavityiselectronegaKveandahractscaKons
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Thiols and Sulfides
• Thiols(RSH),aresulfuranalogsofalcohols• Named with the suffix -thiol • SH group is called “mercapto group” (“capturer of
mercury”)
Thiols: Formation and Reaction
• Fromalkylhalidesbydisplacementwithasulfurnucleophilesuchas–SH• ThealkylthiolproductcanundergofurtherreacKonwiththealkylhalidetogiveasymmetricalsulfide,givingapooreryieldofthethiol
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Sulfides • Sulfides(RSRʹ),aresulfuranalogsofethers
• Named by rules used for ethers, with sulfide in place of ether for simple compounds and alkylthio in place of alkoxy
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Using Thiourea to Form Alkylthiols
• ThiolscanundergofurtherreacKonwiththealkylhalidetogivedialkylsulfides
• Forapurealkylthiolusethiourea(NH2(C=S)NH2)asthenucleophile
• Thisgivesanintermediatealkylisothioureasalt,whichishydrolyzedcleanlytothealkylthiourea
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Oxidation of Thiols to Disulfides
• ReacKonofanalkylthiol(RSH)withbromineoriodinegivesadisulfide(RSSR)
• Thethiolisoxidizedintheprocessandthehalogenisreduced
Sulfides
• Thiolates(RS-)areformedbythereacKonofathiolwithabase
• Thiolatesreactwithprimaryorsecondaryalkylhalidetogivesulfides(RSR’)
• Thiolatesareexcellentnucleophilesandreactwithmanyelectrophiles-Whydoyouthinkthatis?
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Sulfides as Nucleophiles
• Sulfurcompoundsaremorenucleophilicthantheiroxygen-compoundanalogs• 3pelectronsvalenceelectrons(onS)arelessKghtlyheldthan2pelectrons(onO)
• Sulfidesreactwithprimaryalkylhalides(SN2)togivetrialkylsulfoniumsalts(R3S+)
Oxidation of Sulfides
• SulfidesareeasilyoxidizedwithH2O2tothesulfoxide(R2SO)• OxidaKonofasulfoxidewithaperoxyacidyieldsasulfone
(R2SO2)• Dimethylsulfoxide(DMSO)isojenusedasapolaraproKc
solvent
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Spectroscopy of Ethers
• Infrared:C–Osingle-bondstretching1050to1150cm-1overlapsmanyotherabsorpKons.
Spectroscopy of Ethers
• ProtonNMR:HonaCnexttoetherOisshijeddownfieldtoδ3.4toδ4.5• The 1H NMR spectrum of dipropyl ether shows this
signal at δ 3.4 • In epoxides, these H’s absorb at δ 2.5 to δ 3.5 in
their 1H NMR spectra
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Spectroscopy of Ethers
• ProtonNMR:HonaCnexttoetherOisshijeddownfieldtoδ3.4toδ4.5• The 1H NMR spectrum of dipropyl ether shows this
signal at δ 3.4 • In epoxides, these H’s absorb at δ 2.5 to δ 3.5 in
their 1H NMR spectra
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Spectroscopy of Ethers
• ProtonNMR:HonaCnexttoetherOisshijeddownfieldtoδ3.4toδ4.5• The 1H NMR spectrum of dipropyl ether shows this
signal at δ 3.4 • In epoxides, these H’s absorb at δ 2.5 to δ 3.5 in
their 1H NMR spectra • CarbonNMR:C’sinethersexhibitadownfieldshijtoδ50toδ80