CH 17: Alcohols and Phenols

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CH 17 Alcohols and Phenols

• Renee Y. Becker
• CHM 2211
• Valencia Community College

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Alcohols and Phenols

• Alcohols contain an OH group connected to a
  saturated C (sp3)
• They are important solvents and synthesis
  intermediates
• Enols also contain an OH group connected to an
  unsaturated C (sp2)
• Phenols contain an OH group connected to a carbon
  in a benzene ring

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Alcohols and Phenols

• Methanol, CH3OH, called methyl alcohol, is a
  common solvent, a fuel additive, produced in
  large quantities
• Ethanol, CH3CH2OH, called ethyl alcohol, is a
  solvent, fuel, beverage
• Phenol, C6H5OH (phenyl alcohol) has diverse
  uses - it gives its name to the general class of
  compounds

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Naming Alcohols

• General classifications of alcohols based on
  substitution on C to which OH is attached

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IUPAC Rules for Naming Alcohols

• Select 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
  group
• Number substituents according to position on
  chain, listing the substituents in alphabetical
  order

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Many Alcohols Have Common Names

• These are accepted by IUPAC

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Example 1 Give the IUPAC names for these
compounds
3
1
2
4
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Example 2 Draw the following structures

• 2-Ethyl-2-buten-1-ol
• 3-Cyclohexen-1-ol
• 1,4-Pentanediol

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Naming Phenols

• Use phene (the French name for benzene) as the
  parent hydrocarbon name, not benzene
• Name substituents on aromatic ring by their
  position from OH

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Properties of Alcohols and Phenols Hydrogen
Bonding

• The structure around O of the alcohol or phenol
  is similar to that in water, sp3 hybridized
• Alcohols and phenols have much higher boiling
  points than similar alkanes and alkyl halides

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Alcohols Form Hydrogen Bonds

• A positively polarized ?OH hydrogen atom from one
  molecule is attracted to a lone pair of electrons
  on a negatively polarized oxygen atom of another
  molecule
• This produces a force that holds the two
  molecules together
• These intermolecular attractions are present in
  solution but not in the gas phase, thus elevating
  the boiling point of the solution

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Properties of Alcohols and Phenols Acidity and
Basicity

• Weakly basic and weakly acidic
• Alcohols are weak Brønsted bases
• Protonated by strong acids to yield oxonium ions,
  ROH2

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Alchols and Phenols are Weak Brønsted Acids

• Can transfer a proton to water to a very small
  extent
• Produces H3O and an alkoxide ion, RO?, or a
  phenoxide ion, ArO?

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Relative Acidities of Alcohols

• Simple alcohols are about as acidic as water
• Alkyl groups make an alcohol a weaker acid
• The more easily the alkoxide ion is solvated by
  water the more its formation is energetically
  favored
• Steric effects are important

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Stronger acid
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Inductive Effects

• Electron-withdrawing groups make an alcohol a
  stronger acid by stabilizing the conjugate base
  (alkoxide)

Stronger acid
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Generating Alkoxides from Alcohols

• Alcohols 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

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Example 3
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Phenol Acidity

• Phenols (pKa 10) are much more acidic than
  alcohols (pKa 16) due to resonance
  stabilization of the phenoxide ion
• Phenols react with NaOH solutions (but alcohols
  do not), forming soluble salts that are soluble
  in dilute aqueous
• A 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

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Substituted Phenols

• Can be more or less acidic than phenol itself
• An electron-withdrawing substituent makes a
  phenol more acidic by delocalizing the negative
  charge
• Phenols with an electron-donating substituent are
  less acidic because these substituents
  concentrate the charge

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Example 4

• p-Nitrobenzyl alcohol is more acidic than benzyl
  alcohol. Explain.

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Nitro-Phenols

• Phenols with nitro groups at the ortho and para
  positions are much stronger acids
• The pKa of 2,4,6-trinitrophenol is 0.6, a very
  strong acid

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Preparation of Alchols an Overview

• Alcohols are derived from many types of compounds
• The alcohol hydroxyl can be converted to many
  other functional groups
• This makes alcohols useful in synthesis

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Review Preparation of Alcohols by Regiospecific
Hydration of Alkenes

• Hydroboration/oxidation syn, non-Markovnikov
  hydration
• Oxymercuration/reduction Markovnikov hydration

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Preparation of 1,2-Diols

• Review Cis 1,2-diols from hydroxylation of an
  alkene with OsO4 followed by reduction with
  NaHSO3
• In Chapter 18 Trans-1,2-diols from
  acid-catalyzed hydrolysis of epoxides

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Alcohols from Reduction of Carbonyl Compounds

• Reduction of a carbonyl compound in general gives
  an alcohol
• Note that organic reduction reactions add the
  equivalent of H2 to a molecule

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Reduction of Aldehydes and Ketones

• Aldehydes gives primary alcohols
• Ketones gives secondary alcohols

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Catalytic Hydrogenation
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Reduction Reagent Sodium Borohydride

• NaBH4 is not sensitive to moisture and it does
  not reduce other common functional groups
• Lithium aluminum hydride (LiAlH4) is more
  powerful, less specific, and very reactive with
  water
• Both add the equivalent of H-

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Mechanism of Reduction

• The reagent adds the equivalent of hydride to the
  carbon of CO and polarizes the group as well

Not a complete mechanism!!!
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Reduction of Carboxylic Acids and Esters

• Carboxylic acids and esters are reduced to give
  primary alcohols
• LiAlH4 is used because NaBH4 is not effective

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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, RMgX
• Grignard reagents react with carbonyl compounds
  to yield alcohols

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Mechanism of the Addition of a Grignard Reagent

• Grignard reagents act as nucleophilic carbon
  anions (carbanions, R?) in adding to a
  carbonyl group
• The intermediate alkoxide is then protonated to
  produce the alcohol

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Examples of Reactions of Grignard Reagents with
Carbonyl Compounds

• Formaldehyde reacts with Grignard reagents to
  yield primary alcohols.
• Aldehydes react with Grignard reagents to yield
  secondary alcohols.
• Ketones yield tertiary alcohols.

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Examples of Reactions of Grignard Reagents with
Carbonyl Compounds
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Reactions of Esters and Grignard Reagents

• Yields tertiary alcohols in which two of the
  substituents carbon come from the Grignard
  reagent
• Grignard reagents do not add to carboxylic acids
  they undergo an acid-base reaction, generating
  the hydrocarbon of the Grignard reagent

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Grignard Reagents and Other Functional Groups in
the Same Molecule

• Can't be prepared if there are reactive
  functional groups in the same molecule, including
  proton donors

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Synthesis of Diols

• Catalytic hydrogenation

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Some Reactions of Alcohols

• Two general classes of reaction
• At the carbon of the CO bond
• At the proton of the OH bond

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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 ?
  bond
• Specific reagents are needed

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Acid-Catalyzed Dehydration

• Tertiary alcohols are readily dehydrated with
  acid
• Secondary alcohols require severe conditions (75
  H2SO4, 100C) - sensitive molecules don't survive
• Primary alcohols require very harsh conditions
  impractical
• Reactivity is the result of the nature of the
  carbocation intermediate (See Figure 17-5)
• Note that Zaitsevs rule is followed!

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Dehydration with POCl3

• Phosphorus oxychloride in the amine solvent
  pyridine can lead to dehydration of secondary and
  tertiary alcohols at low temperatures
• An E2 via an intermediate ester of POCl2 (see
  Figure 17.6)

pyridine
Follows an E2 mechanism
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Mechanism 1 Dehydration of Alcohol (2? or 3 ?)
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Conversion of Alcohols into Alkyl Halides

• 3 alcohols are converted by HCl or HBr at low
  temperature (Figure 17.7)
• 1 and alcohols are resistant to acid use SOCl2
  or PBr3 by an SN2 mechanism (ether solvent)

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Mechanism 2
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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 maintained
• Alkyl tosylates react like alkyl halides

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Stereochemical Uses of Tosylates

• The SN2 reaction of an alcohol via a tosylate,
  produces inversion at the chiral center
• The SN2 reaction of an alcohol via an alkyl
  halide proceeds with two inversions, giving
  product with same arrangement as starting alcohol

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Oxidation of Alcohols

• Can be accomplished by inorganic reagents, such
  as KMnO4, CrO3, and Na2Cr2O7 or by more
  selective, expensive reagents

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Oxidation of Primary Alcohols

• To aldehyde pyridinium chlorochromate (PCC,
  C5H6NCrO3Cl) in dichloromethane
• Other reagents produce carboxylic acids
• Converts secondary alcohol to ketone

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Oxidation of Primary Alcohols

• Jones Reagent CrO3 in aqueous sulfuric acid.
• Oxidizes primary alcohols to carboxylic acids

All of the oxidations occur via an E2 mechanism.
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Mechanism of Chromic Acid Oxidation

• Alcohol forms a chromate ester followed by
  elimination with electron transfer to give ketone
• The mechanism was determined by observing the
  effects of isotopes on rates

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Oxidation of Secondary Alcohols

• Na2Cr2O7 in aqueous acetic acid is an inexpensive
  oxidizing agent

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Example 5 Predict the major organic product
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Protection of Alcohols

• Hydroxyl groups can easily transfer their proton
  to a basic reagent
• This can prevent desired reactions
• Converting the hydroxyl to a (removable)
  functional group without an acidic proton
  protects the alcohol

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Methods to Protect Alcohols

• Reaction with chlorotrimethylsilane in the
  presence of base yields an unreactive
  trimethylsilyl (TMS) ether
• The ether can be cleaved with acid or with
  fluoride ion to regenerate the alcohol

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Protection-Deprotection
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Preparation and Uses of Phenols

• Industrial process from readily available cumene
• Forms cumene hydroperoxide with oxygen at high
  temperature

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Laboratory Preparation of Phenols

• From aromatic sulfonic acids by melting with NaOH
  at high temperature
• Limited to the preparation of alkyl-substituted
  phenols

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Reactions of Phenols

• The hydroxyl group is a strongly activating,
  making phenols substrates for electrophilic
  halogenation, nitration, sulfonation, and
  FriedelCrafts reactions
• Reaction of a phenol with strong oxidizing agents
  yields a quinone
• Fremy's salt (KSO3)2NO works under mild
  conditions through a radical mechanism

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