Alcohols 10

Overview of Alcohols and Phenols

  • Introduces alcohols, phenols, thiols, and ethers.

  • Discusses classification, properties, and reactivity.

Learning Outcomes

  • Describe the chemical characteristics and reactivity of functional groups.

  • Explain the relationship between drug stereochemistry, molecular shape, properties, reactions, and pharmaceutical uses.

Alcohols and Phenols - Introduction

  • Organic derivatives of water:

    • Water structure: H–O–H.

    • Alcohols: R–O–H.

    • Phenols: Ar–O–H.

    • Ethers: R–O–R′.

  • Corresponding sulfur analogs:

    • Thiols: R–S–H.

    • Thioethers: R–S–R′.

Alcohols and Phenols - Characteristics

  • Alcohols and thiols have -OH or -SH groups on sp3-hybridized carbon.

  • Phenols and thiophenols contain these groups on aromatic rings.

  • Enols and enethiols have these groups on sp2-hybridized carbon

Alcohols and Phenols - Naming

  • Classification of alcohols:

    • Primary (1°)

    • Secondary (2°)

    • Tertiary (3°)

  • IUPAC nomenclature rules:

    1. Identify the longest carbon chain including -OH.

    2. Number from the hydroxyl's nearest end.

    3. Name substituents in alphabetical order with positions noted.

Alcohols and Phenols - Properties

Hydrogen Bonding

  • Higher boiling points due to hydrogen bonding compared to expected values.

Acidity

  • Phenols are far more acidic than alcohols.

  • Acidic comparison:

    • Methanol (pKa = 15.5)

    • Ethanol (pKa = 15.9)

    • Phenol (pKa = 10.0)

  • Stabilization of phenoxide ion increases acidity.

Substituted Phenol

  • Example: 4-nitrophenol is more acidic due to nitro group's resonance stabilization.

Alcohols Reactivity

Dehydration of Alcohols

  • 3° alcohols undergo E1 mechanism:

    1. Protonation of alcohol oxygen.

    2. Loss of water, forming carbocation.

    3. Loss of proton from neighboring carbon.

  • 1° alcohols follow E2 mechanism and require higher temperatures.

Alcohols with Hydrogen Halides

  • Alcohols to alkyl halides reaction:

    • Best with tertiary alcohols.

    • 3°: rapid via SN1 mechanism.

    • 1° & 2°: poor leaving group; convert with SOCl2.

Oxidation of Alcohols

  • 1° alcohols: yield aldehydes or acids based on oxidizing reagent.

  • 2° alcohols: yield ketones.

  • 3° alcohols generally do not oxidize.

Pharmaceutical Examples of Alcohols and Phenols

  • Paracetamol: Acidity and polarity traits.

  • Glyceryl Trinitrate (GTN): Nitration of glycerol; explosive properties and vasodilation.

Thiols

  • Thiols as sulfur analogs of alcohols (R-OH → R-SH).

  • Characterized by strong odor.

  • More acidic than alcohols due to polarizability.

Ethers - Introduction

  • Ethers: organic derivatives of water with both Hs replaced by organic groups (R-O-R’).

Ethers - Nomenclature

  • Named by organic substituents; alkoxy for ethers with functional groups.

Ethers - Geometry

  • Similar geometry to water with tetrahedral bond angles (112° in dimethyl ether).

Ethers - Boiling Points

  • Ethers have low boiling points due to absence of hydrogen bonding.

Ethers - Synthesis

  • Williamson ether synthesis: An alkoxide ion reacts with a primary alkyl halide via SN2.

Ethers - Pharmaceutical Examples

  • Various drugs including anesthetics and pro-drugs like phenacetin and paracetamol.

References

  1. McMurry, J. Organic Chemistry, 9th edition.

  2. Sarker, S. D. & Nahar, L. Chemistry for Pharmacy Students.