Lectures 22 and 23

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Lectures 22 and 23

• Alcohols and Ethers
• Chapter 8

2
Alcohols and Phenols

• Alcohols contain an OH group connected to a a
  saturated C (sp3)
• They are important solvents and synthesis
  intermediates
• 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
• Phenols contain an OH group connected to a carbon
  in a benzene ring
• Phenol, C6H5OH (phenyl alcohol) has diverse
  uses - it gives its name to the general class of
  compounds

3
Naming Alcohols

• General classifications of alcohols based on
  substitution on C to which OH is attached
• Methyl (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),

4
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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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

6
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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Brønsted Acidity Measurements

• The acidity constant, Ka, measure the extent to
  which a Brønsted acid transfers a proton to water
• and pKa ?log Ka
• Relative acidities are more conveniently
  presented on a logarithmic scale, pKa, which is
  directly proportional to the free energy of the
  equilibrium
• Differences in pKa correspond to differences in
  free energy
• Table 8.1 presents a range of acids and their pKa
  values

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pKa Values for Typical OH Compounds
11
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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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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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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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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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

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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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Examples of Reactions of Grignard Reagents with
Carbonyl Compounds
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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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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

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Conversion of Alcohols into Alkyl Halides

• 3 alcohols are converted by HCl or HBr at low
  temperature
• 1 and alcohols are resistant to acid use SOCl2
  or PBr3 by an 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 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 chirality 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

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Oxidation of Secondary Alcohols

• Effective with inexpensive reagents such as
  Na2Cr2O7 in acetic acid
• PCC is used for sensitive alcohols at lower
  temperatures

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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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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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Quinones in Nature

• Ubiquinones mediate electron-transfer processes
  involved in energy production through their redox
  reactions

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Summary -Alcohols

• Synthesis
• Reduction of aldehydes and ketones
• Addition of Grignard reagents to aldehydes and
  ketones
• Reactions
• Conversion to alkyl halides
• Dehydration
• Oxidation

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Summary - Phenols

• Much more acidic (pKa ? 10) than alcohols
• Substitution of the aromatic ring by an
  electron-withdrawing group increases phenol
  acidity
• Substitution by an electron-donating group
  decreases acidity
• Oxidized to quinones
• Quinones are reduced to hydroquinones

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Ethers and Their Relatives

• An ether has two organic groups (alkyl, aryl, or
  vinyl) bonded to the same oxygen atom, ROR?
• Diethyl ether is used industrially as a solvent
• Tetrahydrofuran (THF) is a solvent that is a
  cyclic ether
• Thiols (RSH) and sulfides (RSR?) are sulfur
  (for oxygen) analogs of alcohols and ethers

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Naming Ethers

• Simple ethers are named by identifying the two
  organic substituents and adding the word ether
• If other functional groups are present, the ether
  part is considered an alkoxy substituent

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Structure, Properties, and Sources of Ethers

• ROR tetrahedral bond angle (112 in dimethyl
  ether)
• Oxygen is sp3-hybridized
• Oxygen atom gives ethers a slight dipole moment
• Diethyl ether prepared industrially by sulfuric
  acidcatalyzed dehydration of ethanol also with
  other primary alcohols

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The Williamson Ether Synthesis

• Reaction of metal alkoxides and primary alkyl
  halides and tosylates
• Best method for the preparation of ethers
• Alkoxides prepared by reaction of an alcohol with
  a strong base such as sodium hydride, NaH

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Cyclic Ethers

• Cyclic ethers behave like acyclic ethers, except
  if ring is 3-membered
• Dioxane and tetrahydrofuran are used as solvents

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Epoxides (Oxiranes)

• Three membered ring ether is called an oxirane
  (root ir from tri for 3-membered prefix ox
  for oxygen ane for saturated)
• Also called epoxides
• Ethylene oxide (oxirane 1,2-epoxyethane) is
  industrially important as an intermediate
• Prepared by reaction of ethylene with oxygen at
  300 C and silver oxide catalyst

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Preparation of Epoxides Using a Peroxyacid

• Treat an alkene with a peroxyacid

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Ring-Opening Reactions of Epoxides

• Water adds to epoxides with dilute acid at room
  temperature
• Product is a 1,2-diol (on adjacent Cs vicinal)
• Mechanism acid protonates oxygen and water adds
  to opposite side (trans addition)

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Ethylene Glycol

• 1,2-ethanediol from acid catalyzed hydration of
  ethylene
• Widely used as automobile antifreeze (lowers
  freezing point of water solutions)

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Base-Catalyzed Epoxide Opening

• Strain of the three-membered ring is relieved on
  ring-opening
• Hydroxide cleaves epoxides at elevated
  temperatures to give trans 1,2-diols

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Addition of Grignards to Ethylene Oxide

• Adds CH2CH2OH to the Grignard reagents
  hydrocarbon chain
• Acyclic and other larger ring ethers do not react

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Thiols and Sulfides

• Thiols (RSH), are sulfur analogs of alcohols
• Named with the suffix -thiol
• SH group is called mercapto group (capturer of
  mercury)

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Sulfides

• Sulfides (RSR?), are sulfur analogs of ethers
• 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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Oxidation of Thiols to Disulfides

• Reaction of an alkyl thiol (RSH) with bromine or
  iodine gives a disulfide (RSSR)
• The thiol is oxidized in the process and the
  halogen is reduced

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Sulfides

• Thiolates (RS?) are formed by the reaction of a
  thiol with a base
• Thiolates react with primary or secondary alkyl
  halide to give sulfides (RSR)
• Thiolates are excellent nucleophiles and react
  with many electrophiles

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Sulfides as Nucleophiles

• Sulfur compounds are more nucleophilic than their
  oxygen-compound analogs
• 3p electrons valence electrons (on S) are less
  tightly held than 2p electrons (on O)
• Sulfides react with primary alkyl halides (SN2)
  to give trialkylsulfonium salts (R3S)

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Oxidation of Sulfides

• Sulfides are easily oxidized with H2O2 to the
  sulfoxide (R2SO)
• Oxidation of a sulfoxide with a peroxyacid yields
  a sulfone (R2SO2)
• Dimethyl sulfoxide (DMSO) is often used as a
  polar aprotic solvent

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For Next Class

• Read Chapter 9
• Carbonyl compounds