17.7: Oxidation of Alcohols (2024)

Oxidation States of Carbon

The general idea of oxidation and reduction reactions learned in general chemistry is that when a compound or atom is oxidized it loses electrons, and when it is reduced it gains electrons. In order, to keep track of electrons in organic molecules a oxidation state formalism is used. Oxidation states to not represent the actual charge but it will allow the number of electrons being gained or lost by a particular atom during a reaction.

To calculate the oxidation state of a carbon atom the following rules are used:

1. A C-C bond does not affect the oxidation state of a carbon. So a carbon attached to 4 carbons has an oxidation state of zero.
2. Every C-H bond will decrease the oxidation state of the carbon by 1.
3. Each C-X bond will increase the oxidation state of the carbon by 1. Where X is an electronegative, such as nitrogen, oxygen, sulfur, or a halogen.

When looking at the oxidation states of carbon in the common functional groups shown below it can be said that carbon loses electron density as it becomes more oxidized.

For this section, a simpler way to consider this process is to say that when a carbon atom in an organic compound loses a bond to hydrogen and gains a new bond to a oxygen it has been oxidized. A very commonly example is the oxidation of an alcohol to a ketone or aldehyde. Notice that during this process the carbon atom loses a hydrogen and gains a bond to oxygen.

Oxidation of Alcohols

On of the most important reactions of alcohols is their oxidation to carbonyl containing compounds such as aldehyde, ketones, and carboxylic acid. Typically primary alcohols, depending on the reagent used, produce aldehydes or carboxylic acids during oxidations. Secondary alcohols are oxidized to produce ketones, and tertiary alcohols are usually not affected by oxidations.

Alcohol Oxidizing Agents

Oxidation and reduction reactions always occurs in tandem: when one compound is oxidized, another compound must be reduced. For an alcohol to be oxidized in a reaction there must also be a compound being reduced. This reduced compound is also called the oxidizing agent. For example, chromium trioxide (CrO₃) is a common oxidizing agent used by organic chemists to oxidize a secondary alcohol to a ketone. During this reaction CrO₃ is being reduced to form H₂CrO₃. A common method for oxidizing secondary alcohols to ketones uses chromic acid (H₂CrO₄) as the oxidizing agent. Chromic acid, also known as Jones reagent, is prepared by adding chromium trioxide (CrO₃) to aqueous sulfuric acid.

There is a wide selection of oxidizing agents available for use in the organic chemistry laboratory, each with its own particular properties and uses. In addition to CrO₃, other commonly used oxidizing agents include potassium permanganate (KMnO₄) and sodium dichromate (Na₂Cr₂O₇). ‍Any of these reagents can be used to oxidize secondary alcohols to form ketones and primary alcohols to form carboxylic acids. Tertiary alcohols remain unreactive to oxidation.

Examples

Oxidation of 1^o Alcohols with PCC to form Aldehydes

Pyridinium chlorochromate (PCC) is a milder version of chromic acid. PCC oxidizes 1^o alcohols one rung up the oxidation ladder, turning primary alcohols into aldehydes and secondary alcohols into ketones. Unlike chromic acid, PCC will not oxidize aldehydes to carboxylic acids. Cr(IV) as well as pyridinium chloride are produced as byproducts of this reaction.

Pyridinium chlorochromate (PCC)

Oxidation of 1^o Alcohols with Dess‑Martin Periodinane (DMP) to form Aldehydes

PCC is being replaced in laboratories by Dess‑Martin periodinane (DMP) in dichloromethane solvent, which has several practical advantages over PCC, such as producing higher yields and requiring less rigorous conditions (lower reaction temperature and a nonacidic medium). DMP is named after Daniel Dess and James Martin, who developed it in 1983.

Dess‑Martin periodinane (DMP)

Biological Alcohol Oxidations

There are many biological oxidations that convert a primary or secondary alcohol to a carbonyl compound. These reactions cannot possibly involve the extreme pH conditions and vigorous inorganic oxidants used in typical laboratory oxidations. Rather, they occur at nearly neutral pH values and they all require enzymes as catalysts, which for these reactions usually are called dehydrogenases. An important group of biological oxidizing agents includes the pyridine nucleotides, of which nicotinamide adenine dinucleotide (NAD⁺) is an example. This very complex molecule functions to accept hydride (H:^-) or the equivalent (H⁺+ 2e⁻) from the α carbon of an alcohol. The reduced form of NAD⁺ is abbreviated as NADH and the H:^- is added at the 4-position of the pyridine ring. It is important to note that the hydride adds exclusively to the Re face of the pyridine ring giving NADH a pro-R stereochemistry.

An example of the remarkable specificity of this kind of redox system. One of the last steps in the metabolic breakdown of glucose is the reduction of 2-oxopropanoic (pyruvic) acid to L-2-hydroxypropanoic (lactic) acid. The reverse process is oxidation of L-lactic acid. The enzyme lactic acid dehydrogenase catalyses this reaction, and it functions only with the L-enantiomer of lactic acid. During this reaction a base removes the alcohol hydrogen. The resulting alkoxide ion then forms the C=O bond causing a hydride ion to transfer to NAD⁺.

The Structure of NAD+

From an outside source. Convert mechanism to use lactic acid.

Another example is provided by one of the steps in metabolism by way of the Krebs citric acid cycle, is the oxidation of L-2-hydroxy-butanedioic (L-malic) acid to 2-oxobutanedioic (oxaloacetic) acid. This enzyme functions only with L-malic acid:

Exercises