Chapters 7 & 8: Alcohols, Phenols, Ethers - Synthesis & Reactions

Alcohols, Phenols, Ethers, and Thiols

  • Alcohols: Contain an OH group connected to a saturated carbon (sp3). They are important solvents and synthesis intermediates.
    • Methanol (CH3OH), or methyl alcohol, is a common solvent and fuel additive produced in large quantities.
    • Ethanol (CH3CH2OH), or ethyl alcohol, is a solvent, fuel, and beverage.
  • Phenols: Contain an OH group connected to a carbon in a benzene ring.
    • Phenol (C6H5OH), or phenyl alcohol, has diverse uses and gives its name to the general class of compounds.

Phenols

  • Phenols are ingredients found in cloves, vanilla, nutmeg, and mint.
  • Examples include: Vanillin, Eugenol, Thymol, Isoeugenol.

Ethers and Thiols

  • Ethers: Have two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom (R–O–R').
    • Diethyl ether is used industrially as a solvent.
    • Tetrahydrofuran (THF) is a cyclic ether used as a solvent.
  • Thiols (R–S–H) and sulfides (R–S–R') are sulfur analogs of alcohols and ethers.

Thiols

  • Methanethiol is found in oysters and cheese.
  • Ethanethiol.
  • 2-Propanethiol.
  • 2-Propene-1-thiol is found in garlic.
  • 1-Propanethiol is found in onions.

Classification of Alcohols

  • Classification depends on the number of organic groups (R) bonded to the hydroxyl-bearing carbon.
    • Primary (1°) alcohol: The –OH group is on a carbon atom bonded to one R group.
    • Secondary (2°) alcohol: The –OH group is on a carbon atom bonded to two R groups.
    • Tertiary (3°) alcohol: The –OH group is on a carbon atom bonded to three R groups.

Properties

  • The structure around the oxygen atom in alcohols, ethers, and phenols is similar to that in water (sp^3 hybridized).
  • Alcohols and phenols have much higher boiling points than similar alkanes and alkyl halides.
  • The oxygen atom gives ethers a slight dipole moment.
  • Alcohols and phenols have higher boiling points than expected due to hydrogen bonding.
  • Thiols do not typically form hydrogen bonds because sulfur is not sufficiently electronegative.

Relative Acidity of Alcohols and Phenols

  • Acidity constants (pK_a) vary for different alcohols and phenols.
  • Examples (with pK_a values):
    • (CH3)3COH: 18.00 (Weaker acid)
    • CH2CH2OH: 16.00
    • HOH (water): 15.74
    • CH_3OH: 15.54
    • CF3CH2OH: 12.43
    • p-Aminophenol: 10.46
    • p-Methoxyphenol: 10.21
    • p-Methylphenol: 10.17
    • Phenol: 9.89
    • p-Chlorophenol: 9.38
    • p-Bromophenol: 9.35
    • p-Nitrophenol: 7.15
    • 2,4,6-Trinitrophenol: 0.60 (Stronger acid)

Alcohol Acidity: Inductive Effect

  • Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide).
  • Example: CF3 groups stabilize alkoxide and lower the pKa.

Generating Alkoxides from Alcohols

  • Alcohols are weak acids, requiring a strong base to form an alkoxide (e.g., NaH, NaNH_2, Grignard reagents (RMgX)).
  • Alkoxides are bases used as reagents in organic chemistry.

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.
  • Electron-withdrawing substituents make a phenol more acidic by delocalizing the negative charge.
  • Electron-donating substituents make a phenol less acidic because they concentrate the charge.

Synthesis/Reactions of Alcohols

  • Alcohols can be synthesized from alkenes, carboxylic acids, ketones, esters, alkyl halides, aldehydes, and ethers.

Preparation of Alcohols: Hydration of Alkenes

  • Hydration of alkenes produces alcohols using an acid catalyst (e.g., H3PO4).
  • Epoxidation of alkenes followed by treatment with H_3O^+ yields 1,2-diols.

Preparation of Alcohols: Reduction of Carbonyl

  • Reduction of a carbonyl compound generally gives an alcohol.
  • Organic reduction reactions add the equivalent of H_2 to a molecule.

Mechanism of Reduction

  • The reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group.

Reduction of Aldehydes and Ketones

  • Aldehydes give primary alcohols upon reduction.
  • Ketones give secondary alcohols upon reduction.

Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents

  • Grignard formation: R–X + Mg → R–MgX (Grignard reagent)

Mechanism of Grignard Reagents

  • Grignard reagents react with carbonyl compounds to form alkoxide ions, which are then protonated to form alcohols (RMgX).

Preparation from Alkyl Halides

  • Alkyl halides react with hydroxide ions to form alcohols.
    • CH3-Br + HO^- → HO-CH3 + Br^-

Reactions of Alcohols

  • Two general classes of reactions:
    • At the carbon of the C–O bond.
    • At the proton of the O–H bond.

Dehydration of Alcohols to Yield Alkenes

  • The general reaction forms an alkene from an alcohol through the loss of O–H and H from the neighboring C–H to give a \pi bond.
  • Specific reagents are needed.

Acid-Catalyzed Dehydration

  • Tertiary alcohols are readily dehydrated with acid.
  • Secondary alcohols require more severe conditions (75% H2SO4, 100°C).
  • Primary alcohols require very harsh conditions, which is often impractical.
  • In the elimination, the more highly substituted alkene product predominates (Zaitsev’s Rule).

Conversion of Alcohols into Alkyl Halides

  • 3° alcohols are converted by HCl or HBr at low temperature.
  • 1° and 2° alcohols are resistant to acid; use SOCl2 or PBr3.

Oxidation of Alcohols

  • Can be accomplished by inorganic reagents such as KMnO4, CrO3, and Na2Cr2O_7, or by more selective reagents.

Oxidation of Primary Alcohols

  • To aldehyde: pyridinium chlorochromate (PCC, C5H6NCrO_3Cl) in dichloromethane.
  • Other reagents produce carboxylic acids.

Oxidation of Secondary Alcohols

  • Effective with inexpensive reagents such as Na2Cr2O_7 in acetic acid.
  • PCC is used for sensitive alcohols at lower temperatures.

The Williamson Ether Synthesis

  • Reaction of metal alkoxides and primary alkyl halides and tosylates.
  • Alkoxides are prepared by the reaction of an alcohol with a strong base such as sodium hydride, NaH.

Acidic Cleavage of Ethers

  • Ethers are generally unreactive.
  • Strong acid will cleave an ether at elevated temperature.