Pharmaceutical Organic Chemistry 1 - Alcohols and Amines

Pharmaceutical Organic Chemistry 1 (PC 102) - Lecture 6: Alcohols and Amines

• Alcohols (ROH): Classification

  • Classified based on the type of carbon atom bonded to the -OH group.
  • Primary (1°): Carbon bonded to one other carbon and the -OH group.
  • Secondary (2°): Carbon bonded to two other carbons and the -OH group.
  • Tertiary (3°): Carbon bonded to three other carbons and the -OH group.

• Alcohols: Classification based on Hydroxyl Groups:

  • Monohydric: One -OH group (e.g., ethanol).
  • Dihydric: Two -OH groups (e.g., ethylene glycol).
  • Trihydric: Three -OH groups (e.g., glycerol).
  • Polyhydric: More than three -OH groups (e.g., sorbitol).

• Nomenclature of Alcohols:

  • Common Name: Alkyl group + "alcohol".
  • IUPAC Name:
    • Identify the longest carbon chain containing the -OH group.
    • Number the chain from the end closest to the -OH group.
    • Use the appropriate number to indicate the position of the -OH.
    • Name substituents and give their numbers.

• Preparation of Alcohols -From alkenes (See lecture 3) -From alkyl halides via nucleophilic substitution. -From aldehydes and ketones (See lecture 5) via reduction and Grignard reagents. -From carboxylic acids (See lecture 5) -From epoxides.

• Physical Properties of Alcohols -Lower alcohols are water-miscible due to hydrogen bonding. -Increasing hydrocarbon chain length decreases water solubility (more hydrophobic). -Alcohols have higher boiling points than comparable alkanes due to intermolecular hydrogen bonding. -Branching decreases boiling point as it reduces the surface area for intermolecular interaction.

• Reactions of Alcohols -Reaction with active metals (Na, Li): Produces sodium/lithium alkoxides and hydrogen gas (CH3CH2ONa + H₂). -Ester formation: Reaction with carboxylic acids to form esters (e.g., acetic acid + methanol → methyl acetate). Reactivity: 1° > 2° > 3°. -Oxidation: -Primary alcohols to aldehydes and then to carboxylic acids (using CrO3/H2SO4, K2Cr2O7/H2SO4 or KMnO4). - Secondary alcohols to ketones (using CrO3/H2SO4). -Tertiary alcohols do not readily undergo oxidation. -Reaction with Hydrogen Halides: Produces alkyl halides and water (R-OH + HX --> R-X + H₂O). Reactivity order: allyl/benzyl > 3° > 2° > 1°

• Amines: Classification

  • Classified based on the number of alkyl groups attached to the nitrogen atom.
  • 1° Amine: one alkyl group bonded to the nitrogen atom.
  • 2° Amine: two alkyl groups bonded to the nitrogen atom.
  • 3° Amine: three alkyl groups bonded to the nitrogen atom.

• Nomenclature of Amines: -Derived from the corresponding alkane name with the suffix -amine.

• Preparation of Amines: -Partial reduction of nitrogenous compounds (using LiAlH₄) -Hofmann degradation (for 1° Amines)

• Physical Properties: -Boiling points increase with increasing molecular mass. -Primary and secondary amines can form hydrogen bonds, resulting in higher boiling points than comparable alkanes, especially compared to aldehydes, ketones, ethers and alcohols.

• Reactions of Amines: -Salt formation with acids (e.g., reacting with sulfuric acid produces a salt) -Acylation. -Reaction with nitrous acid(primary aliphatic amines will form alkyl diazonium ions).