Alcohols and Phenols

Nomenclature and Classification

Alcohols are organic compounds containing a hydroxyl group (-OH) attached to a saturated carbon atom. Phenols have the -OH group attached to an aromatic ring. Classification is based on the number of alkyl groups attached to the carbon bearing the hydroxyl group:

• Primary (1°) alcohol: The carbon with the -OH is attached to one other carbon.

• Secondary (2°) alcohol: The carbon with the -OH is attached to two other carbons.

• Tertiary (3°) alcohol: The carbon with the -OH is attached to three other carbons.

Naming: Use the longest chain containing the -OH group as the parent, number to give the -OH the lowest possible number, and use the suffix -ol.

Preparation of Alcohols

• Hydroboration-Oxidation of Alkenes: Converts alkenes to alcohols via anti-Markovnikov addition.

• Oxymercuration-Reduction: Converts alkenes to alcohols via Markovnikov addition.

• Reduction of Carbonyl Compounds: Aldehydes and ketones can be reduced to alcohols using sodium borohydride (NaBH4) or lithium aluminum hydride (LiAlH4).

• Organometallic Reagents: Grignard reagents (RMgX) or organolithium reagents react with carbonyl compounds to form alcohols after hydrolysis.

• Esters with Organometallics: Reaction of esters with excess Grignard or organolithium reagents yields tertiary alcohols.

Dehydration of Alcohols

Alcohols can be dehydrated in strong acid (e.g., H2SO4) to form alkenes, following Zaitsev's Rule (the more substituted alkene is favored). The mechanism is typically E1 for secondary and tertiary alcohols.

• Mechanism: Protonation of -OH, loss of water to form carbocation, elimination of H+ to form alkene.

Conversion to Alkyl Halides

• Reaction with HX: Tertiary alcohols react with HX (e.g., HCl, HBr) via SN1 mechanism.

• SOCl2 and PBr3: Primary and secondary alcohols can be converted to alkyl chlorides and bromides, respectively, via SN2 mechanism.

Oxidation of Alcohols

• Primary alcohols: Oxidized to aldehydes (Dess-Martin periodinane) or carboxylic acids (Cr(VI) reagents).

• Secondary alcohols: Oxidized to ketones (Dess-Martin or Cr(VI)).

• Tertiary alcohols: Generally do not undergo oxidation under these conditions.

Protecting Groups

• Trimethylsilyl (TMS) Ether: Used to protect alcohols during synthesis. Removed with fluoride ion (e.g., TBAF).

Ethers and Epoxides

Nomenclature and Preparation

• Naming: Simple ethers are named as "alkyl alkyl ether" or using the "-oxy" suffix.

• Williamson Ether Synthesis: Reaction of an alkoxide ion with a primary alkyl halide (RX) to form an ether. Limited to primary RX to avoid elimination.

Cleavage of Ethers

• Acidic Cleavage: Ethers react with HBr or HI to yield alkyl halides and alcohols. Regiochemistry depends on the structure of the ether.

Preparation of Carboxylic Acids (from Ethers Chapter)

• Oxidation of Alcohols or Aldehydes: Converts to carboxylic acids.

• Hydrolysis of Nitriles: Nitriles can be hydrolyzed to carboxylic acids.

• Organometallics with CO2: Grignard reagents react with CO2 to form carboxylic acids after acid workup.

Carboxylic Acids and Nitriles

Nomenclature

• Carboxylic Acids: Named with the suffix -oic acid. Common names: formic acid (C1), acetic acid (C2).

• Nitriles: Named with the suffix -nitrile or as a derivative of the parent acid.

Electronic Effects on Acidity

• Electron-withdrawing groups lower pKa (increase acidity).

• Electron-donating groups raise pKa (decrease acidity).

Preparation of Carboxylic Acids

• Hydrolysis of Nitriles: Converts nitriles to carboxylic acids.

• Organometallics with CO2: Grignard reagents react with CO2 to form carboxylic acids.

• Limitations: Highly substituted alkyl halides do not react efficiently with CN- to form nitriles.

Reactions of Nitriles

• Hydrolysis: Nitriles hydrolyze to amides and then to acids.

• Reaction with Organometallics: Forms carbonyl compounds (e.g., ketones) after hydrolysis.

Carboxylic Acid Derivatives: Acyl Transfer Reactions

Nomenclature

• Acyl Halides: Replace -ic acid with -yl chloride.

• Anhydrides: Replace acid with anhydride.

• Esters: Name alkyl group attached to oxygen, then parent acid with -ate suffix.

• Amides: Replace -ic acid with -amide.

Reactivity of Acid Derivatives

Preparation and Reactions

• Acid Chlorides: Prepared from carboxylic acids using SOCl2. React with water (hydrolysis), alcohols (ester formation), and amines (amide formation).

• Fischer Esterification: Carboxylic acid reacts with alcohol in acid to form ester. Mechanism required: Protonation, nucleophilic attack, proton transfers, loss of water, deprotonation.

• Acid Anhydrides: React with alcohols to form esters and with amines to form amides.

• Esters: Undergo esterification and hydrolysis (mechanisms required), and react with amines to form amides.

• Amides: Hydrolyzed to carboxylic acids (mechanism required).

General Mechanism for Nucleophilic Acyl Substitution

All acyl derivatives undergo nucleophilic acyl substitution, where a nucleophile replaces the leaving group attached to the acyl carbon.

Key Equations and Mechanisms

• Hydroboration-Oxidation:

• Oxymercuration-Reduction:

• Reduction of Carbonyls:

• Grignard Addition:

• Dehydration (E1):

• Oxidation of Alcohols:

• Williamson Ether Synthesis:

• Hydrolysis of Nitriles:

• Fischer Esterification:

Summary Table: Reactivity of Carboxylic Acid Derivatives

Additional info: Mechanisms for key transformations (e.g., Fischer esterification, nucleophilic acyl substitution) are essential for understanding reactivity and should be practiced in detail.