Notes on Alcohols and Their Synthesis

Old Ways to Make Alcohols

Acid-Catalyzed Hydration of Alkenes

  • Process: Water adds to the double bond of alkenes.
  • Rule: Follows Markovnikov's rule, where the more substituted carbon receives the hydroxyl group.
  • Example: 2,3-Dimethyl-2-butene reacts to give 2,3-Dimethyl-2-butanol (90% yield).

Hydroboration-Oxidation of Alkenes

  • Process: Hydrogen (H) and hydroxyl (OH) is added to the double bond oppositely to Markovnikov's rule.
  • Properties: The addition is syn. Rearrangements do not occur.
  • Example:
    1. Start with alkene (e.g., 1-Decene).
    2. Use B2H6 in diglyme followed by H2O2 in NaOH to yield corresponding alcohols.

Hydrolysis of Alkyl Halides

  • Process: Useful for alkyl halides that are resistant to E2 eliminations.
  • Relevance: Rarely practiced for alcohol synthesis since alkyl halides are typically synthesized from alcohols.

Reactions of Grignard and Organolithium Reagents

  • Method: React with aldehydes and ketones to form alcohols, creating new C-C bonds.
  • Types of Alcohols: Can produce primary, secondary, or tertiary alcohols.
  • Example: 2,4,6-Trimethylbenzyl alcohol (78% yield) produced from reaction with Grignard reagent and ketone.

Reduction of Carbonyl Compounds

  • Hydride Reagents: Used to reduce C=O compounds into alcohols.
    • Sodium Borohydride (NaBH4): Effective for aldehydes and ketones.
    • Lithium Aluminum Hydride (LiAlH4): More powerful, can react with esters and carboxylic acids.
    • Catalytic Hydrogenation: Converts alkenes to alcohols under pressure.

Making Alcohols from Epoxides

  • Reagents: Grignard or LiAlH4 adds to epoxides to produce alcohols.
  • Steps:
    1. Epoxides treated with Grignard reagent in a solvent (diethyl ether).
    2. Product is then treated with H3O+ to yield the desired alcohol.

Making Diols from Dicarbonyl Compounds

  • Diol Formation: Reduction of carbonyl compounds can lead to diols.
    • Example with Benzil: Benzil reduced using NaBH4 creates a diol.

Making Esters from Alcohols

  • Fischer Esterification: Interaction of carboxylic acid with alcohol under acid catalysis to form an ester.
    • Mechanism Overview:
      1. Protonation of the carbonyl.
      2. Formation of a tetrahedral intermediate.
      3. Loss of water to form the ester.

Oxidation of Alcohols

  • Primary Alcohols: Oxidized to aldehydes and subsequently to carboxylic acids
  • Secondary Alcohols: Oxidized to ketones, cannot be further oxidized.
  • Tertiary Alcohols: Generally resistant to oxidation due to lack of C-H bonds.

Biological Oxidations

  • Enzymatic oxidation of ethanol to acetaldehyde catalyzed by alcohol dehydrogenase, utilizing NAD+ as a cofactor.

Thiols (Mercaptans)

  • Properties: Contain -SH group, more volatile and acidic than comparable alcohols.
  • Preparation & Reactions:
    • Formed via SN2 reaction with hydrosulfide.
    • Oxidation can yield disulfides.

Reactions of Thiols

  • Can undergo oxidation reactions, forming disulfide bridges.
  • Use with alkyl halides for synthesis via nucleophilic substitution reactions.

Practice Problems

  • Write structures of esters formed in reactions involving alcohols and acids or anhydrides.
  • Discuss oxidation pathways for alcohols and their expected products.