Chapter 12: Oxidation and Reduction of Organic Molecules

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Oxidation and Reduction in Organic Chemistry

Overview of Oxidation and Reduction

Oxidation and reduction are fundamental concepts in organic chemistry, describing changes in the bonding of carbon atoms to hydrogen and heteroatoms (especially oxygen). These processes are central to the transformation of organic molecules.

Oxidation: Increase in the number of C–O bonds or decrease in the number of C–H bonds.
Reduction: Increase in the number of C–H bonds or decrease in the number of C–O bonds.

Example: The oxidation of a primary alcohol to an aldehyde and then to a carboxylic acid involves the sequential increase in C–O bonds.

Reductions of Organic Molecules

Types of Reductions

There are three main types of reductions, differing in how hydrogen is added to the substrate:

Hydrogen gas (H2) as reducing agent: Often with a metal catalyst (e.g., Pd, Pt, Ni).
Dissolving metal reductions: Addition of two protons and two electrons to a substrate (e.g., Na/NH3).
Hydride and proton addition: Addition of hydride (H–) and a proton (H+), as with LiAlH4 or NaBH4.

Catalytic Hydrogenation

Mechanism and Application

Catalytic hydrogenation is the addition of H2 to a multiple bond in the presence of a metal catalyst, resulting in the formation of C–H bonds.

Catalysts: Pd, Pt, or Ni, usually adsorbed onto an inert solid (e.g., charcoal).
Syn addition: Both hydrogens add to the same face of the double or triple bond.
Heat of hydrogenation: Used to measure the relative stability of alkenes. Less stable alkenes release more energy upon hydrogenation.

Equation:

Catalytic Hydrogenation Mechanism

H2 adsorbs to the catalyst surface, partially or completely cleaving the H–H bond.
The alkene binds to the metal surface.
Two H atoms are transferred sequentially to the alkene, forming the alkane.

Reactivity order: Less substituted alkenes hydrogenate faster than more substituted ones.

Reduction of Alkynes

Methods of Reduction

Alkynes can be reduced in three main ways:

Complete reduction: Addition of two equivalents of H2 forms an alkane.
Partial reduction (syn): Addition of one equivalent of H2 with Lindlar catalyst forms a cis-alkene.
Partial reduction (anti): Dissolving metal reduction (Na/NH3) forms a trans-alkene.

Catalytic Hydrogenation of Alkynes

Lindlar catalyst: Pd on CaCO3 with Pb(OAc)4 and quinoline; stops reduction at the cis-alkene stage.
Equation:

Dissolving Metal Reduction of Alkynes

Uses sodium in liquid ammonia (Na/NH3).
Produces trans-alkenes via a radical anion intermediate.
Mechanism: Electron transfer, protonation, electron transfer, protonation.

Reduction of Polar C–X σ Bonds with LiAlH4

LiAlH4 is a strong reducing agent that donates hydride (H–) to polar C–X bonds (X = O, N, halogen).

Reduces alkyl halides, epoxides, and carbonyl compounds to hydrocarbons or alcohols.
Hydride attacks the less substituted carbon in epoxides.

Oxidation Reactions

Types of Oxidation

Epoxidation: Formation of an epoxide from an alkene using a peroxyacid (e.g., mCPBA).
Dihydroxylation: Addition of two hydroxy groups to a double bond, forming a 1,2-diol (glycol).
Oxidative cleavage: Breaking of C=C or C≡C bonds to form carbonyl compounds or carboxylic acids.

Epoxidation

Alkene reacts with a peroxyacid (e.g., mCPBA) to form an epoxide and a carboxylic acid.
Equation:

Dihydroxylation

Addition of two –OH groups to a double bond.
Syn dihydroxylation: Both –OH groups add to the same side (e.g., with KMnO4 or OsO4).
Anti dihydroxylation: Achieved via epoxidation followed by ring opening with OH– or H2O.

Mechanism of Syn Dihydroxylation

OsO4 or KMnO4 adds to the alkene, forming a cyclic intermediate, which is then hydrolyzed to a 1,2-diol.
NMO can be used to regenerate OsO4 catalyst.

Anti Dihydroxylation via Epoxide

Epoxidation of alkene, followed by ring opening with aqueous acid or base, yields trans-1,2-diols (enantiomers).

Oxidative Cleavage

Ozonolysis of Alkenes

Ozone (O3) cleaves C=C bonds to form carbonyl compounds (aldehydes or ketones).
Reductive workup (Zn/H2O or (CH3)2S) is used to isolate products.
Equation:

Oxidative Cleavage of Alkynes

Internal alkynes yield two carboxylic acids.
Terminal alkynes yield a carboxylic acid and CO2.

Oxidation of Alcohols

Primary, Secondary, and Tertiary Alcohols

Primary alcohols: Oxidized to aldehydes (PCC) or carboxylic acids (K2Cr2O7/H2SO4).
Secondary alcohols: Oxidized to ketones.
Tertiary alcohols: Generally resistant to oxidation (no reaction under normal conditions).

Mechanisms

Primary alcohols: Oxidation with PCC yields aldehyde; with K2Cr2O7 yields carboxylic acid.
Secondary alcohols: Oxidation with PCC or K2Cr2O7 yields ketone.
Biological oxidation: NAD+ acts as an oxidant in enzymatic reactions.

The Sharpless Epoxidation—An Enantioselective Reaction

Sharpless Epoxidation

Enantioselective epoxidation of allylic alcohols using a chiral catalyst (e.g., (+)- or (–)-diethyl tartrate, Ti(OiPr)4, and t-butyl hydroperoxide).
Produces epoxides with high enantiomeric excess (up to 95%).
The stereochemistry of the product depends on the chirality of the tartrate used.

Synthesis Using Asymmetric Epoxidation

Sharpless epoxidation is a key step in the synthesis of chiral insect pheromones and other biologically active molecules.
Allows for the preparation of enantiomerically pure compounds.

Summary Table: Oxidation and Reduction of Organic Molecules

Transformation	Reagent(s)	Product(s)	Notes
Alkene to Alkane	H2, Pd/C	Alkane	Syn addition
Alkyne to Alkene (cis)	H2, Lindlar catalyst	Cis-alkene	Partial reduction
Alkyne to Alkene (trans)	Na/NH3	Trans-alkene	Dissolving metal reduction
Alkene to Epoxide	mCPBA	Epoxide	Syn addition
Alkene to 1,2-diol (syn)	OsO4, KMnO4	1,2-diol	Syn addition
Alkene to 1,2-diol (anti)	Epoxidation, then H2O/OH–	1,2-diol	Anti addition
Alkene to Carbonyls	O3, Zn/H2O	Aldehyde/ketone	Ozonolysis
Alkyne to Carboxylic Acids	O3, H2O	Carboxylic acids	Oxidative cleavage
1° Alcohol to Aldehyde	PCC	Aldehyde	Mild oxidation
1° Alcohol to Carboxylic Acid	K2Cr2O7, H2SO4	Carboxylic acid	Strong oxidation
2° Alcohol to Ketone	PCC, K2Cr2O7	Ketone	Oxidation
Allylic Alcohol to Epoxide	Sharpless reagent	Chiral epoxide	Enantioselective