Chapter 17: Alcohols and PhenolsBased on McMurrys Organic Chemistry, 7th edition

*Alcohols and PhenolsAlcohols contain an OH group connected to a a saturated C (sp3)They are important solvents and synthesis intermediatesPhenols contain an OH group connected to a carbon in a benzene ringMethanol, CH3OH, called methyl alcohol, is a common solvent, a fuel additive, produced in large quantitiesEthanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beveragePhenol, C6H5OH (phenyl alcohol) has diverse uses - it gives its name to the general class of compoundsOH groups bonded to vinylic, sp2-hybridized carbons are called enols

*Why this Chapter?To begin to study oxygen-containing functional groups

These groups lie at the heart of biological chemistry

*17.1 Naming Alcohols and PhenolsGeneral classifications of alcohols based on substitution on C to which OH is attachedMethyl (C has 3 Hs), Primary (1) (C has two Hs, one R), secondary (2) (C has one H, two Rs), tertiary (3) (C has no H, 3 Rs),

*IUPAC Rules for Naming AlcoholsSelect the longest carbon chain containing the hydroxyl group, and derive the parent name by replacing the -e ending of the corresponding alkane with -ol Number the chain from the end nearer the hydroxyl groupNumber substituents according to position on chain, listing the substituents in alphabetical order

*Naming PhenolsUse phenol (the French name for benzene) as the parent hydrocarbon name, not benzeneName substituents on aromatic ring by their position from OH

*17.2 Properties of Alcohols and PhenolsThe structure around O of the alcohol or phenol is similar to that in water, sp3 hybridizedAlcohols and phenols have much higher boiling points than similar alkanes and alkyl halidesA positively polarized OH hydrogen atom from one molecule is attracted to a lone pair of electrons on a negatively polarized oxygen atom of another moleculeThis produces a force that holds the two molecules togetherThese intermolecular attractions are present in solution but not in the gas phase, thus elevating the boiling point of the solution

*Properties of Alcohols and Phenols: Acidity and Basicity Weakly basic and weakly acidicAlcohols are weak Brnsted basesProtonated by strong acids to yield oxonium ions, ROH2+

*Alcohols and Phenols are Weak Brnsted AcidsCan transfer a proton to water to a very small extentProduces H3O+ and an alkoxide ion, RO, or a phenoxide ion, ArO

*Acidity MeasurementsThe acidity constant, Ka, measures the extent to which a Brnsted acid transfers a proton to water[A] [H3O+] Ka = and pKa = log Ka[HA] Relative acidities are more conveniently presented on a logarithmic scale, pKa, which is directly proportional to the free energy of the equilibriumDifferences in pKa correspond to differences in free energyTable 17.1 presents a range of acids and their pKa values

*pKa Values for Typical OH Compounds

*Relative Acidities of AlcoholsSimple alcohols are about as acidic as waterAlkyl groups make an alcohol a weaker acidThe more easily the alkoxide ion is solvated by water the more its formation is energetically favoredSteric effects are important

*Inductive EffectsElectron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide)

*Generating Alkoxides from AlcoholsAlcohols are weak acids requires a strong base to form an alkoxide such as NaH, sodium amide NaNH2, and Grignard reagents (RMgX) Alkoxides are bases used as reagents in organic chemistry

*Phenol AcidityPhenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16) due to resonance stabilization of the phenoxide ionPhenols react with NaOH solutions (but alcohols do not), forming salts that are soluble in dilute aqueous solutionA phenolic component can be separated from an organic solution by extraction into basic aqueous solution and is isolated after acid is added to the solution

*Nitro-PhenolsPhenols with nitro groups at the ortho and para positions are much stronger acids

*17.3 Preparation of Alcohols: A ReviewAlcohols are derived from many types of compoundsThe alcohol hydroxyl can be converted to many other functional groupsThis makes alcohols useful in synthesis

*Review: Preparation of Alcohols by Regiospecific Hydration of AlkenesHydroboration/oxidation: syn, non-Markovnikov hydration Oxymercuration/reduction: Markovnikov hydration

*1,2-DiolsReview: Cis-1,2-diols from hydroxylation of an alkene with OsO4 followed by reduction with NaHSO3Trans-1,2-diols from acid-catalyzed hydrolysis of epoxides

*17.4 Alcohols from Reduction of Carbonyl Compounds Reduction of a carbonyl compound in general gives an alcoholNote that organic reduction reactions add the equivalent of H2 to a molecule

*Reduction of Aldehydes and Ketones Aldehydes gives primary alcoholsKetones gives secondary alcohols

*Reduction Reagent: Sodium BorohydrideNaBH4 is not sensitive to moisture and it does not reduce other common functional groupsLithium aluminum hydride (LiAlH4) is more powerful, less specific, and very reactive with waterBoth add the equivalent of H-

*Mechanism of ReductionThe reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group as well

*Reduction of Carboxylic Acids and Esters Carboxylic acids and esters are reduced to give primary alcoholsLiAlH4 is used because NaBH4 is not effective

*17.5 Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgXGrignard reagents react with carbonyl compounds to yield alcohols

*Reactions of Grignard Reagents with Carbonyl Compounds

*Reactions of Esters and Grignard ReagentsYields tertiary alcohols in which two of the substituents carbon come from the Grignard reagentGrignard reagents do not add to carboxylic acids they undergo an acid-base reaction, generating the hydrocarbon of the Grignard reagent

*Grignard Reagents and Other Functional Groups in the Same MoleculeCan't be prepared if there are reactive functional groups in the same molecule, including proton donors

*Mechanism of the Addition of a Grignard ReagentGrignard reagents act as nucleophilic carbon anions (carbanions, : R) in adding to a carbonyl groupThe intermediate alkoxide is then protonated to produce the alcohol

*17.6 Reactions of Alcohols Conversion of alcohols into alkyl halides:3 alcohols react with HCl or HBr by SN1 through carbocation intermediate1 and 2 alcohols converted into halides by treatment with SOCl2 or PBr3 via SN2 mechanism

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*Conversion of Alcohols into Tosylates Reaction with p-toluenesulfonyl chloride (tosyl chloride, p-TosCl) in pyridine yields alkyl tosylates, ROTos Formation of the tosylate does not involve the CO bond so configuration at a chirality center is maintainedAlkyl tosylates react like alkyl halides

*Stereochemical Uses of TosylatesThe SN2 reaction of an alcohol via a tosylate, produces inversion at the chirality centerThe SN2 reaction of an alcohol via an alkyl halide proceeds with two inversions, giving product with same arrangement as starting alcohol

*Dehydration of Alcohols to Yield Alkenes The general reaction: forming an alkene from an alcohol through loss of O-H and H (hence dehydration) of the neighboring CH to give bondSpecific reagents are needed

*Acid- Catalyzed DehydrationTertiary alcohols are readily dehydrated with acidSecondary alcohols require severe conditions (75% H2SO4, 100C) - sensitive molecules don't survivePrimary alcohols require very harsh conditions impracticalReactivity is the result of the nature of the carbocation intermediate

*Dehydration with POCl3Phosphorus oxychloride in the amine solvent pyridine can lead to dehydration of secondary and tertiary alcohols at low temperaturesAn E2 via an intermediate ester of POCl2 (see Figure 17.7)

*Conversion of Alcohols into Esters

*17.7 Oxidation of Alcohols Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents

*Oxidation of Primary AlcoholsTo aldehyde: pyridinium chlorochromate (PCC, C5H6NCrO3Cl) in dichloromethaneOther reagents produce carboxylic acids

*Oxidation of Secondary AlcoholsEffective with inexpensive reagents such as Na2Cr2O7 in acetic acidPCC is used for sensitive alcohols at lower temperatures

*Mechanism of Chromic Acid OxidationAlcohol forms a chromate ester followed by elimination with electron transfer to give ketoneThe mechanism was determined by observing the effects of isotopes on rates

*17.8 Protection of Alcohols Hydroxyl groups can easily transfer their proton to a basic reagentThis can prevent desired reactionsConverting the hydroxyl to a (removable) functional group without an acidic proton protects the alcohol

*Methods to Protect AlcoholsReaction with chlorotrimethylsilane in the presence of base yields an unreactive trimethylsilyl (TMS) etherThe ether can be cleaved with acid or with fluoride ion to regenerate the alcohol

*Protection-DeprotectionAn example of TMS-alcohol protection in a synthesis

*17.9 Phenols and Their UsesIndustrial process from readily available cumeneForms cumene hydroperoxide with oxygen at high temperatureConverted into phenol and acetone by acid

*17.10 Reactions of Phenols The hydroxyl group is a strongly activating, making phenols substrates for electrophilic halogenation, nitration, sulfonation, and FriedelCrafts reactionsReaction of a phenol with strong oxidizing agents yields a quinoneFremy's salt [(KSO3)2NO] works under mild conditions through a radical mechanism

*Quinones in NatureUbiquinones mediate electron-transfer processes involved in energy production through their redox reactions

*17.11 Spectroscopy of Alcohols and Phenols Characteristic OH stretching absorption at 3300 to 3600 cm1 in the infraredSharp absorption near 3600 cm-1 except if H-bonded: then broad absorption 3300 to 3400 cm1 rangeStrong CO stretching absorption near 1050 cm1 (See Figure 17.11)Phenol OH absorbs near 3500 cm-1

*Nuclear Magnetic Resonance Spectroscopy 13C NMR: C bonded to OH absorbs at a lower field, 50 to 80 1H NMR: electron-withdrawing effect of the nearby oxygen, absorbs at 3.5 to 4 (See Figure 17-13)Usually no spin-spin coupling between OH proton and neighboring protons on C due to exchange reactions with moisture or acidsSpinspin splitting is observed between protons on the oxygen-bearing carbon and other neighbors Phenol OH protons absorb at 3 to 8

*Mass Spectrometry Alcohols undergo alpha cleavage, a CC bond nearest the hydroxyl group is broken, yielding a neutral radical plus a charged oxygen-containing fragmentAlcohols undergo dehydration to yield an alkene radical anion

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