Oxidation and Reduction Reactions in Organic Chemistry

Oxidation

Introduction to Oxidation

• Oxidation involves adding oxygen, removing hydrogen/electrons.

• More $C-O$ bonds signify oxidation; more $C-H$ bonds signify reduction.

• Carbon oxidation levels: Alkane (most reduced) $\rightarrow$ Alcohol $\rightarrow$ Aldehyde/Ketone $\rightarrow$ Carboxylic Acid $\rightarrow$ Carbon Dioxide (most oxidized).

Synthesis of Carbonyl Compounds

• Methods: Alcohol oxidation or oxidative cleavage of alkenes.

Oxidation of Alcohols

• Primary alcohols ($1^o$) oxidize to aldehydes, then carboxylic acids.

• Secondary alcohols ($2^o$) oxidize to ketones.

• Tertiary alcohols ($3^o$) resist oxidation.

Oxidizing Agents

• Examples: Peracids (for $C=C$ bonds), Chromium(VI) compounds (for alcohols), Osmium tetroxide (for alkenes), Ozone (for alkenes—ozonolysis).

Metals in High Oxidation States: Cr(VI) and Mn(VII)

• Reagents: Chromic anhydride, Sodium/Potassium dichromate, Potassium permanganate.

• Primary alcohols oxidize to carboxylic acids; secondary to ketones.

• Aldehydes easily over-oxidize to carboxylic acids.

Jones Oxidation

• Chromium(VI) oxidizes primary alcohols to carboxylic acids and secondary to ketones. Not for acid-sensitive molecules or aldehyde synthesis.

Synthesis of Aldehydes

• PDC and PCC oxidize primary alcohols to aldehydes; secondary to ketones.

Mild Oxidants

• TPAP and Dess-Martin periodinane (DMP) chemoselectively oxidize primary alcohols to aldehydes.

Swern Oxidation

• Mild method for oxidizing primary alcohols to aldehydes and secondary alcohols to ketones using DMSO.

Swern Oxidation Mechanism

1. Step 1: Generation of Dimethyl Sulfonium Salt

   • DMSO reacts with oxalyl chloride to form dimethyl sulfonium chloride, releasing $CO$ and $CO_2$.

2. Step 2: Oxidation of Alcohol

   • Alcohol reacts with dimethyl sulfonium salt, forming an ylide, which leads to aldehyde and dimethyl sulfide.

Oxidation of Alkenes

Ozonolysis

• Ozone ($O_3$) cycloadds to alkenes. Reductive workup gives aldehydes/ketones; oxidative gives ketones/carboxylic acids.

Osmium Tetraoxide/Sodium Periodate

• $OsO<em>4$ gives syn 1,2-diols; $NaIO</em>4$ cleaves diols.

Potassium Permanganate

• $KMnO_4$ under acidic conditions gives two $C=O$ compounds. Secondary alkenes yield carboxylic acids; tertiary, ketones.

Oxidative Cleavage of Alkynes

• Terminal alkynes yield a $C=O$ compound and carbon dioxide ($CO_2$).

Reduction

Introduction to Reduction

• Reduction involves adding electrons, achieved via hydrogen addition, proton/electron addition, or hydride/proton addition.

• Reactions reverse oxidation: Carboxylic acid $\rightarrow$ primary alcohol, etc.

Two General Classes

• Reduction of carbonyl compounds and alkenes/alkynes.

Reducing Agents

• Examples: $H<em>2$, $Pd-C$ (for alkenes), $NaBH</em>4$ and $LiHBH<em>4$ (for $C=O$), $LiAlH</em>4$, $NaCNBH_3$.

Reduction of Carbonyl Compounds

• Reactivity: aldehydes > ketones > esters > carboxylic acids > amides.

Hydride Reagents

Sodium Borohydride ($NaBH_4$)

• Reduces aldehydes/ketones to alcohols.

Lithium Borohydride ($LiBH_4$)

• Reduces esters as well.

Lithium Aluminium Hydride ($LiAlH_4$)

• Reduces most carbonyl compounds, including amides to amines and carboxylic acids to alcohols.

Diisobutylaluminium Hydride (DIBAL-H)

• Reduces esters/nitriles to aldehydes and lactones to lactols.

Borane ($BH_3$)

• Reduces amides and carboxylic acids.

Rosenmund Reduction

• Hydrogenolysis of $C-Cl$ to $C-H$ using $Pd$ on $BaSO_4$. Reduces acyl chlorides to aldehydes.

Reduction of Imines

• Iminium ions reduce to amines using sodium cyanoborohydride $(Na(CN)BH_3)$.

Reductive Amination

• Borohydride reagents synthesize amines from aldehydes/ketones.

Chemoselectivity and Protective Groups

• Chemoselectivity: functional group reactivity; Regioselectivity: where it reacts; Stereoselectivity: stereoisomer formation.

Protective Groups

• Used when functional groups interfere. Acetals protect aldehydes/ketones but are acid labile.