Alcohols and Phenols - Ashley (Piekarski · Alcohols and Phenols • Methanol, CH 3 OH, called...
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2/8/16 1 Chapter 17- Alcohols and Phenols Alcohols and Phenols • Alcohols contain an OH group connected to a a saturated C (sp 3 ) • They are important solvents and synthesis intermediates • Phenols contain an OH group connected to a carbon in a benzene ring
Transcript of Alcohols and Phenols - Ashley (Piekarski · Alcohols and Phenols • Methanol, CH 3 OH, called...
2/8/16
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Chapter 17- Alcohols and Phenols
Alcohols and Phenols
• AlcoholscontainanOHgroupconnectedtoaasaturatedC(sp3)
• Theyareimportantsolventsandsynthesisintermediates
• PhenolscontainanOHgroupconnectedtoacarboninabenzenering
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Alcohols and Phenols
• Methanol,CH3OH,calledmethylalcohol,isacommonsolvent,afueladdiGve,producedinlargequanGGes
• Ethanol,CH3CH2OH,calledethylalcohol,isasolvent,fuel,beverage
• Phenol,C6H5OH(“phenylalcohol”)hasdiverseuses-itgivesitsnametothegeneralclassofcompounds
• OHgroupsbondedtovinylic,sp2-hybridizedcarbonsarecalledenols
Why do I care, Dr. P?
• Tobegintostudyoxygen-containingfuncGonalgroups
• Thesegroupslieattheheartofbiologicalchemistry
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Nomenclature
• GeneralclassificaGonsofalcoholsbasedonsubsGtuGononCtowhichOHisaPached
• Methyl(Chas3H’s),• Primary(1°)(ChastwoH’s,oneR),• Secondary(2°)(ChasoneH,twoR’s),• TerGary(3°)(ChasnoH,3R’s),
IUPAC Rules for Naming Alcohols
1) Selectthelongestcarbonchaincontainingthehydroxylgroup,andderivetheparentnamebyreplacingthe-eendingofthecorrespondingalkanewith-ol
2) Numberthechainfromtheendnearerthehydroxylgroup3) NumbersubsGtuentsaccordingtoposiGononchain,lisGngthe
subsGtuentsinalphabeGcalorder
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Naming Phenols
• Use“phenol”(theFrenchnameforbenzene)astheparenthydrocarbonname,notbenzene
• NamesubsGtuentsonaromaGcringbytheirposiGonfromOH
Learning check
• GivethecorrectIUPACnamesforthefollowingcompounds.
OH
2-ethyl-4-nitrophenol
O2NHO H
Cl
(S,Z)-6-chlorohept-5-en-3-ol
1. OsO4, pyridine2. NaHSO3, H2O
1. Hg(OAc)2, H2O2. NaBH4
MgBr
+
O1. ether
2. H3O+
O
OH1. LiAlH4, ether2. H3O+
OHH
1. p-TosCl, pyridine
2. NaOCH3, CH3OH
OH
2-ethyl-4-nitrophenol
O2NHO H
Cl
(S,Z)-6-chlorohept-5-en-3-ol
1. OsO4, pyridine2. NaHSO3, H2O
1. Hg(OAc)2, H2O2. NaBH4
MgBr
+
O1. ether
2. H3O+
O
OH1. LiAlH4, ether2. H3O+
OHH
1. p-TosCl, pyridine
2. NaOCH3, CH3OH
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Properties of Alcohols and Phenols
• ThestructurearoundOofthealcoholorphenolissimilartothatinwater,sp3hybridized
• Alcoholsandphenolshavemuchhigherboilingpointsthansimilaralkanesandalkylhalides• Whydoyouthinkalcoholsandphenolshavehighboilingpoints?
Properties of Alcohols and Phenols: Acidity and Basicity
• Weaklybasicandweaklyacidic• AlcoholsareweakBrønstedbases• Protonatedbystrongacidstoyieldoxoniumions,ROH2
+
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Alcohols and Phenols are Weak Brønsted Acids
• Cantransferaprotontowatertoaverysmallextent
• ProducesH3O+andanalkoxideion,RO-,oraphenoxideion,ArO-
Acidity Measurements
• Theacidityconstant,Ka,measurestheextenttowhichaBrønstedacidtransfersaprotontowater [A-][H3O+]Ka=—————andpKa=-logKa [HA]
• RelaGveacidiGesaremoreconvenientlypresentedonalogarithmicscale,pKa,whichisdirectlyproporGonaltothefreeenergyoftheequilibrium
• WhatistherelaGonshipbetweenpKaandthestrengthoftheacid?
• DifferencesinpKacorrespondtodifferencesinfreeenergy
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pKa Values for Typical OH Compounds
Relative Acidities of Alcohols
• Simplealcoholsareaboutasacidicaswater• Alkylgroupsmakeanalcoholaweakeracid• ThemoreeasilythealkoxideionissolvatedbywaterthemoreitsformaGonisenergeGcallyfavored
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Inductive Effects
• Electron-withdrawinggroupsmakeanalcoholastrongeracidbystabilizingtheconjugatebase(alkoxide)
Generating Alkoxides from Alcohols
• Alcoholsareweakacids–requiresastrongbasetoformanalkoxidesuchasNaH,sodiumamideNaNH2,andGrignardreagents(RMgX)
• Alkoxidesarebasesusedasreagentsinorganicchemistry
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Phenol Acidity
• Phenols(pKa~10)aremuchmoreacidicthanalcohols(pKa~16)duetoresonancestabilizaGonofthephenoxideion
• PhenolsreactwithNaOHsoluGons(butalcoholsdonot),formingsaltsthataresolubleindiluteaqueoussoluGon• Whyisthisimportantinthelaboratory?
Nitro-Phenols
• PhenolswithnitrogroupsattheorthoandparaposiGonsaremuchstrongeracids
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Learning check
• Thefollowingdataforisomericfour-carbonalcoholsshowthatthereisadecreaseinboilingpointwithincreasingsubsGtuGonoftheOH-bearingcarbon.Howmightyouaccountforthistrend?• 1-butanol, bp 117.5°C • 2-butanol, bp 99.5°C • 2-methyl-2-propanol, bp 82.2°C
Preparation of Alcohols: A Review
• Alcoholsarederivedfrommanytypesofcompounds• ThealcoholcanbeconvertedtomanyotherfuncGonalgroups
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Preparation of Alcohols
• Whataresomewaysyoucanpreparealcoholsfromalkenes?
Review: Preparation of Alcohols by Regiospecific Hydration of Alkenes
• HydroboraGon/oxidaGon:syn,non-MarkovnikovhydraGon• OxymercuraGon/reducGon:MarkovnikovhydraGon
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1,2-Diols
• Cis-1,2-diolsfromhydroxylaGonofanalkenewithOsO4followedbyreducGonwithNaHSO3
• Trans-1,2-diolsfromacid-catalyzedhydrolysisofepoxides
Learning check
• PredicttheproductsofthefollowingreacGons:
OH
2-ethyl-4-nitrophenol
O2NHO H
Cl
(S,Z)-6-chlorohept-5-en-3-ol
1. OsO4, pyridine2. NaHSO3, H2O
1. Hg(OAc)2, H2O2. NaBH4
MgBr
+
O1. ether
2. H3O+
O
OH1. LiAlH4, ether2. H3O+
OHH
1. p-TosCl, pyridine
2. NaOCH3, CH3OH
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Alcohols from Reduction of Carbonyl Compounds
• ReducGonofacarbonylcompoundingeneralgivesanalcohol
• NotethatorganicreducGonreacGonsaddtheequivalentofH2toamolecule
Reduction of Aldehydes and Ketones
• Aldehydesproduceprimaryalcohols
• Ketonesproducesecondaryalcohols
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Reducing Reagent: Sodium Borohydride
• NaBH4isnotsensiGvetomoistureanditdoesnotreduceothercommonfuncGonalgroups
• Lithiumaluminumhydride(LiAlH4)ismorepowerful,lessspecific,andveryreacGvewithwater
• Bothaddtheequivalentof“H-”
Mechanism of Reduction
• ThereagentaddstheequivalentofhydridetothecarbonofC=Oandpolarizesthegroupaswell
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Reduction of Carboxylic Acids and Esters
• Carboxylicacidsandestersarereducedtogiveprimaryalcohols
• LiAlH4isusedbecauseNaBH4isnoteffecGve
Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents
• Alkyl,aryl,andvinylichalidesreactwithmagnesiuminetherortetrahydrofurantogenerateGrignardreagents,RMgX
• Grignardreagentsreactwithcarbonylcompoundstoyieldalcohols
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Reactions of Grignard Reagents with Carbonyl Compounds
Reactions of Esters and Grignard Reagents
• YieldsterGaryalcoholsinwhichtwoofthesubsGtuentscomefromtheGrignardreagent
• Grignardreagentsdonotaddtocarboxylicacids–theyundergoanacid-basereacGon,generaGngthehydrocarbonoftheGrignardreagent
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Grignard Reagents and Other Functional Groups in the Same Molecule
• Can'tbepreparediftherearereacGvefuncGonalgroupsinthesamemolecule,includingprotondonors
Mechanism of the Addition of a Grignard Reagent
• Grignardreagentsactasnucleophiliccarbonanions(carbanions,:R-)inaddingtoacarbonylgroup
• Theintermediatealkoxideisthenprotonatedtoproducethealcohol
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Learning check
• PredicttheproductofthefollowingreacGonsbelow.
OH
2-ethyl-4-nitrophenol
O2NHO H
Cl
(S,Z)-6-chlorohept-5-en-3-ol
1. OsO4, pyridine2. NaHSO3, H2O
1. Hg(OAc)2, H2O2. NaBH4
MgBr
+
O1. ether
2. H3O+
O
OH1. LiAlH4, ether2. H3O+
OHH
1. p-TosCl, pyridine
2. NaOCH3, CH3OH
Reactions of Alcohols
• Conversionofalcoholsintoalkylhalides:- 3˚alcoholsreactwithHClorHBrbySN1throughcarbocaGonintermediate
- 1˚and2˚alcoholsconvertedintohalidesbytreatmentwithSOCl2orPBr3viaSN2mechanism
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Conversion of Alcohols into Tosylates
• ReacGonwithp-toluenesulfonylchloride(tosylchloride,p-TosCl)inpyridineyieldsalkyltosylates,ROTos
• FormaGonofthetosylatedoesnotinvolvetheC–ObondsoconfiguraGonatachiralitycenterismaintained
• Alkyltosylatesreactlikealkylhalides
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Stereochemical Uses of Tosylates
• TheSN2reacGonofanalcoholviaatosylate,producesinversionatthechiralitycenter
• TheSN2reacGonofanalcoholviaanalkylhalideproceedswithtwoinversions,givingproductwithsamearrangementasstarGngalcohol
Dehydration of Alcohols to Yield Alkenes
• ThegeneralreacGon:forminganalkenefromanalcoholthroughlossofO-HandH(hencedehydraGon)oftheneighboringC–Htogiveπbond
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Acid- Catalyzed Dehydration
• TerGaryalcoholsarereadilydehydratedwithacid-whyis2-methyl-2-butenethemajorproduct?
• SecondaryalcoholsrequireseverecondiGons(75%H2SO4,100°C)-sensiGvemoleculesdon'tsurvive
• PrimaryalcoholsrequireveryharshcondiGons–impracGcal
• ReacGvityistheresultofthenatureofthecarbocaGonintermediate
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Dehydration with POCl3
• PhosphorusoxychlorideintheaminesolventpyridinecanleadtodehydraGonofsecondaryandterGaryalcoholsatlowtemperatures
• AnE2viaanintermediateesterofPOCl2
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Conversion of Alcohols into Esters
Learning check
• PredicttheproductforthefollowingreacGonbelow.
OH
2-ethyl-4-nitrophenol
O2NHO H
Cl
(S,Z)-6-chlorohept-5-en-3-ol
1. OsO4, pyridine2. NaHSO3, H2O
1. Hg(OAc)2, H2O2. NaBH4
MgBr
+
O1. ether
2. H3O+
O
OH1. LiAlH4, ether2. H3O+
OHH
1. p-TosCl, pyridine
2. NaOCH3, CH3OH
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Oxidation of Alcohols
• Canbeaccomplishedbyinorganicreagents,suchasKMnO4,CrO3,andNa2Cr2O7orbymoreselecGve,expensivereagents
Oxidation of Primary Alcohols
• Toaldehyde:pyridiniumchlorochromate(PCC,C5H6NCrO3Cl)indichloromethane
• Otherreagentsproducecarboxylicacids
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Oxidation of Secondary Alcohols
• EffecGvewithinexpensivereagentssuchasNa2Cr2O7inaceGcacid
• PCCisusedforsensiGvealcoholsatlowertemperatures
Mechanism of Chromic Acid Oxidation
• AlcoholformsachromateesterfollowedbyeliminaGonwithelectrontransfertogiveketone
• Themechanismwasdeterminedbyobservingtheeffectsofisotopesonrates
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Protection of Alcohols
• Hydroxylgroupscaneasilytransfertheirprotontoabasicreagent
• ThiscanpreventdesiredreacGons• ConverGngthehydroxyltoa(removable)funcGonalgroupwithoutanacidicprotonprotectsthealcohol
Methods to Protect Alcohols
• ReacGonwithchlorotrimethylsilaneinthepresenceofbaseyieldsanunreacGvetrimethylsilyl(TMS)ether
• Theethercanbecleavedwithacidorwithfluorideiontoregeneratethealcohol
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Protection-Deprotection
• AnexampleofTMS-alcoholprotecGoninasynthesis
Reactions of Phenols
• ThehydroxylgroupisastronglyacGvaGng,makingphenolssubstratesforelectrophilichalogenaGon,nitraGon,sulfonaGon,andFriedel–CratsreacGons
• ReacGonofaphenolwithstrongoxidizingagentsyieldsaquinone
• Fremy'ssalt[(KSO3)2NO]worksundermildcondiGonsthrougharadicalmechanism
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Quinones in Nature
• Ubiquinonesmediateelectron-transferprocessesinvolvedinenergyproducGonthroughtheirredoxreacGons
Spectroscopy of Alcohols and Phenols
• CharacterisGcO–HstretchingabsorpGonat3300to3600cm-1intheinfrared
• SharpabsorpGonnear3600cm-1exceptifH-bonded:thenbroadabsorpGon3300to3400cm-1range
• StrongC–OstretchingabsorpGonnear1050cm-1
• PhenolOHabsorbsnear3500cm-1
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IR spectrum
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Nuclear Magnetic Resonance Spectroscopy
• 13CNMR:Cbondedto⎯OHabsorbsatalowerfield,δ50to80
• 1HNMR:electron-withdrawingeffectofthenearbyoxygen,absorbsatδ3.5to4(SeeFigure17-13)• Usuallynospin-spincouplingbetweenO–HprotonandneighboringprotonsonCduetoexchangereacGonswithmoistureoracids
• Spin–spinspliungisobservedbetweenprotonsontheoxygen-bearingcarbonandotherneighbors
• PhenolO–Hprotonsabsorbatδ3to8
NMR spectrum
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Mass Spectrometry
• Alcoholsundergoalphacleavage,aC–Cbondnearestthehydroxylgroupisbroken,yieldinganeutralradicalplusachargedoxygen-containingfragment
• AlcoholsundergodehydraGontoyieldanalkeneradicalanion
Mass Spectrum
