Alcohols and Phenols: Key Vocabulary

Alcohols: Structure and Properties

• Alcohols contain a hydroxyl group (-OH) bonded to an sp^3-hybridized carbon atom.
• Naming: Identify the longest chain containing the hydroxyl group as the parent chain.
• Alcohols possess both hydrophilic (OH group) and hydrophobic (alkyl group) regions.
• Solubility:
  • Small alcohols like methanol, ethanol, and n-propanol are miscible with water (mix in any ratio).
  • Solubility refers to the limited amount of a substance that can dissolve in a specific volume of water at room temperature.
  • n-Butanol is soluble in water (to a limited extent).

Acidity of Alcohols and Alkoxides

• Alkoxide Ions: The conjugate base formed by deprotonating an alcohol.
• pK_a values for alcohols typically range from 15 to 18.
• Deprotonation: Alcohols are commonly deprotonated using strong bases like sodium hydride (NaH) or alkali metals (Na, Li, K).
• Factors Affecting Acidity:
  • Resonance: Stabilization of the conjugate base (alkoxide ion) through resonance.
  • Induction: Electron-withdrawing groups increase acidity by stabilizing the negative charge on the alkoxide ion.
  • Solvation Effects: Solvation of the alkoxide ion can influence its stability and, therefore, the acidity of the alcohol.
• Phenols:
  • Phenol (hydroxybenzene) forms a conjugate base called phenolate or phenoxide ion.

Synthesis of Alcohols

• Substitution Reactions:
  • Primary Substrates: Favor S_N2 conditions for substitution reactions to form alcohols.
  • Tertiary Substrates: Favor S_N1 conditions.
• Addition Reactions:
  • Acid-Catalyzed Hydration: Addition of water across an alkene using an acid catalyst.
  • Oxymercuration-Demercuration: A two-step process involving mercury(II) acetate and sodium borohydride to add water across an alkene.
  • Hydroboration-Oxidation: Addition of borane (BH_3) to an alkene followed by oxidation with hydrogen peroxide to yield an alcohol with anti-Markovnikov regioselectivity.
• Reduction of Carbonyl Compounds
  • Alcohols can be synthesized by reducing carbonyl groups (C=O) with reducing agents.
  • Reduction: A decrease in the oxidation state of a carbon atom.
  • Reactivity: Lithium aluminum hydride (LiAlH4) is a stronger reducing agent than sodium borohydride (NaBH4).
    • LiAlH_4 reduces carboxylic acids and esters.
    • NaBH_4 typically reduces aldehydes and ketones but not carboxylic acids or esters.

Diols: Synthesis and Reactions

• Diols: Compounds containing two hydroxyl groups.
• Synthesis:
  • Reduction of Diketones: Reduction of diketones using reducing agents such as LiAlH4 or NaBH4.
  • Dihydroxylation of Alkenes: Addition of two hydroxyl groups across a double bond.
    • Syn Dihydroxylation: Addition of two hydroxyl groups on the same side of the alkene (e.g., using OsO4).
    • Anti Dihydroxylation: Addition of two hydroxyl groups on opposite sides of the alkene (e.g., via epoxidation followed by ring-opening).

Oxidation Reactions

• Oxidation: Involves an increase in the oxidation state of a carbon atom.

Grignard Reagents in Alcohol Synthesis

• Grignard Reagents: Carbon nucleophiles (R-MgX) that react with electrophiles, particularly carbonyl compounds.
• Reactions:
  • Ketones and Aldehydes: Grignard reagents attack the carbonyl carbon to produce alcohols.
  • Esters: React with Grignard reagents to yield tertiary alcohols with the introduction of two R groups from the Grignard reagent.

Protecting Groups

• Protecting Groups: Used to temporarily mask a functional group to prevent unwanted reactions.
• Trimethylsilyl (TMS) Group: A common protecting group for alcohols.
  • Application: Used to protect an alcohol during a Grignard reaction where the alcohol's acidic proton would interfere.
  • Removal: Easily removed after the Grignard reaction.

Phenols: Properties and Uses

• Phenol (Hydroxybenzene): Used as a precursor in the synthesis of pharmaceuticals and other commercially important compounds.

Reactions of Alcohols

• Reactions with Hydrogen Halides (HX):
  • Tertiary Alcohols: Undergo S_N1 reactions with HX.
  • Primary and Secondary Alcohols: Undergo SN2 reactions with HX, SOCl2, or PBr_3, or via tosylation followed by nucleophilic attack.
• Elimination Reactions:
  • Tertiary Alcohols: Undergo E1 elimination when treated with sulfuric acid (H2SO4).
  • E2 Process: Requires converting the hydroxyl group into a better leaving group (tosylate or alkyl halide).
• Oxidation Reactions:
  • Primary Alcohols: Can be oxidized twice to yield a carboxylic acid.
  • Secondary Alcohols: Oxidized once to give a ketone.
  • Tertiary Alcohols: Do not undergo oxidation due to the absence of an α-hydrogen.
  • Common Oxidizing Reagent: Chromic acid (H2CrO4), formed from chromium trioxide (CrO3) or sodium dichromate (Na2Cr2O7) in aqueous acidic solution.
• PCC (Pyridinium Chlorochromate):
  • Converts primary alcohols into aldehydes.
• Swern Oxidation and DMP (Dess-Martin Periodinane) Oxidation:
  • Alternative methods for converting primary alcohols into aldehydes.

Biological Aspects

• NADH and NAD+:
  • NADH: A biological reducing agent that delivers hydride ions (like NaBH4 or LiAlH4).
  • NAD+: An oxidizing agent.
  • Roles: Both play critical roles in biological systems, including the citric acid cycle and ATP synthesis.

Quinones

• Phenols undergo oxidation to form quinones.
• Quinones are important in biological systems due to their redox properties, particularly in cellular respiration.

Synthesis Strategies

• Key Considerations:
  • Changes to the carbon skeleton.
  • Changes to the functional group(s).