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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