OIA1012 PHENOLS, ETHERS, ESTERS

Definition of Phenols

Aromatic compounds with one or more hydroxyl groups attached to the benzene ring.

Phenol Acidity

More acidic than alcohols due to resonance stabilization of the phenoxide ion.

Substituent Effects on Phenol Acidity

- Electron-withdrawing groups stabilise phenoxide ion → increase acidity.

- Electron-donating groups destabilise phenoxide ion → decrease acidity.

Nitration of Phenols

Produces ortho- and para-nitrophenols, enhanced by electron-rich aromatic rings.

Phenol Halogenation

Phenols react readily with halogens to produce halogenated derivatives (e.g., trichlorophenol).

Diazo Coupling

Phenols react with diazonium salts to form azo dyes, useful in characterization.

Phenol Radical Reactions

Forms phenoxy radicals, stabilized by resonance.

Phenols as Antioxidants

Phenolic compounds like BHA prevent oxidation in pharmaceutical formulations.

Ethers Definition

Compounds with an oxygen atom bonded to two alkyl or aryl groups.

Physical Properties of Ethers

Low boiling points, poor water solubility, chemically inert.

Ether reactions: Acid-catalyzed decomposition

React with strong halogen acids (HBr/HCl) to promote decomposition of ethers at room temperature followed by nucleophilic attack at the a-carbon atom by halide ion.

If ethers are heated with halogen acids, both alkyl groups become alkyl halides

Ether reactions: Peroxide formation

Ethers readily form peroxides by light-catalyzed air oxidation

Ethers in Pharmaceuticals

Used as solvents and anesthetics (e.g., diethyl ether).

Epoxides Reactivity

Highly reactive three-membered cyclic ethers, used in sterilization (e.g., ethylene oxide).

Epoxide Reactions

React with alcohols or amines to form glycol ethers or alkanolamines.

Thioethers

Sulfur analogs of ethers, found in drugs like chlorpromazine.

Esters Definition

Derived from carboxylic acids and alcohols.

Ester Physical Properties

- Low molecular weight esters have fruity odors.

- Lipophilic nature increases drug solubility.

Hydrolysis of Esters

- Acid hydrolysis: Produces alcohol and carboxylic acid.

- Base hydrolysis (saponification): Produces carboxylate salt.

Aminolysis

Esters react with ammonia & amines to give amides

Other reactions of esters

Esters react with hydrazine to form acid hydrazides & with hydroxylamine to form hydroxamic acids

Esterases

Enzymes that hydrolyze esters in the body (e.g., acetylcholinesterase).

Lipid Esters

- Fats: Saturated glycerol esters. Fluids at room temperature.

- Oils: Unsaturated glycerol esters. Solid or semi-solid at room temperature.

Waxes

Mixture of esters of long-chain carboxylic acids and alcohols (sterols), used in ointments and tablet coatings. Hard, brittle, non-greasy solids at room temperature

Phospholipids

Glycerol-based esters, key components of cell membranes.

Sphingolipids

Found in nerve tissue, derived from sphingosine.

Ester in Drug Formulations

Prodrugs like chloramphenicol palmitate mask unpleasant tastes.

Trans Fats

Partially hydrogenated vegetable oils containing trans isomers, linked to heart disease.

Ester Reductions: Hydride reduction

Hydride reduction with LiAlH4 produces primary alcohol

Ester Reductions: Catalytic reduction

Catalytic hydrogenation of esters produces alcohols (e.g., lauryl alcohol from coconut oil).