Overview

In this lesson, the oxidation of alcohols is discussed in depth. The various reagents used for oxidation of primary and secondary alcohols are detailed, and their mechanism of action is provided.

The process of oxidation in a chemical reaction is observed in any of the three forms:

Oxidation is the opposite process of reduction, and hence, as carbonyls are reduced to alcohols, alcohols are oxidized to carbonyls. However, the oxidation of alcohols to carbonyls is dictated by the number of hydrogens present on the α-carbon linked to the hydroxyl group in the starting alcohol. Accordingly, while primary alcohols can be oxidized to aldehydes and further carboxylic acids, the secondary alcohols can only be oxidized to their corresponding ketones. Since there are no α-protons, tertiary alcohols cannot be oxidized. During the oxidation, there is a corresponding increase in the oxidation state of the central species.

Reagents and Mechanism

A popular reagent is the Jones reagent, a chromium trioxide solution in aqueous sulfuric acid in the presence of acetone. The reaction proceeds via an intermediate chromate ester and a subsequent E2 pathway to produce the carbonyl species. However, while the Jones oxidation ends at a ketone for secondary alcohol, the oxidation is repeated for primary alcohol resulting in a carboxylic acid. The other popular reagent used for oxidation is potassium permanganate. Similar to the Jones reagent, potassium permanganate is also a strong oxidizing agent converting the primary alcohol to a carboxylic acid. Hence, when an aldehyde is desired, a selective reagent like pyridinium chlorochromate or PCC should be used.

One major drawback of using these reagents is that they involve the higher oxidation states of chromium that are toxic. Accordingly, greener alternatives like Swern oxidation and Dess-martin oxidation have been designed. They employ reagents such as oxalyl chloride, dimethyl sulfoxide (DMSO), triethylamine, and dichloromethane, which are relatively non-toxic to convert the primary alcohols into aldehydes and secondary alcohols into ketones. In their mechanism, the Swern oxidation advances via an alkyl-sulfonium compound, while the Dess–Martin oxidation proceeds via a periodinane intermediate.

Procedure

As with the reduction of carbonyls to alcohols, the outcome of the oxidation of alcohols to carbonyls depends on the number of alpha protons present in the starting alcohol. Here, the oxidation state of the alpha carbon linked to the hydroxyl group is increased.

A primary alcohol has two hydrogen atoms attached to the alpha carbon atom. Hence, the molecule can be oxidized twice: first to an aldehyde, and then to a carboxylic acid. Here, the reaction is aided by Jones reagent: a chromium trioxide solution in aqueous sulfuric acid in the presence of acetone.

The mechanism of the reaction has two steps. In the first step, the alcohol and chromic acid react to form a chromate ester. Subsequently, the chromate ion leaves via an E2 pathway to form the carbon−oxygen pi bond.

The aldehyde is then hydrated and the process is repeated to generate a carboxylic acid. Similarly, the oxidation of a primary alcohol with potassium permanganate ultimately yields a carboxylic acid.

In either case, it is difficult to isolate the intermediate aldehyde. Achieving this requires a more selective reagent like pyridinium chlorochromate, or PCC.

Both Jones reagent and PCC also transform secondary alcohols into ketones. However, as chromium(VI) compounds are highly toxic, oxalyl chloride, DMSO, triethylamine, and dichloromethane are greener alternatives to convert primary alcohols into aldehydes and secondary alcohols into ketones.

Swern oxidation employs oxalyl chloride and DMSO to create a reactive chlorosulfonium species, which first reacts with the alcohol to form an alkylsulfonium compound. In step two, deprotonation with an organic base like triethylamine leads to the oxidized product.

In Dess–Martin oxidation, the alcohol reacts with the hypervalent Dess–Martin periodinane, or DMP, in dichloromethane. This proceeds via a periodinane intermediate to form the corresponding aldehyde or ketone.

However, none of these reagents can oxidize tertiary alcohols, which have no alpha hydrogen atom.