The Malaprade reaction is an oxidation reaction in which a vicinal diol, or 1,2-diol, is cleaved to form carbonyl compounds. It was first reported by French chemist Léon Malaprade in 1928. ^[1–4]

General Reaction

A vicinal diol contains two hydroxyl groups on adjacent carbon atoms. ^[1,2]

The general reaction can be represented as:

R¹R²C(OH)–C(OH)R³R⁴ –[HIO₄]→ R¹R²C=O + O=CR³R⁴

The carbon–carbon bond joining the two hydroxyl-bearing carbons is broken, and a carbonyl group forms at each carbon.

One can predict the products by examining what is attached to each hydroxyl-bearing carbon:

• If a hydroxyl-bearing carbon has a hydrogen atom, it generally forms an aldehyde.
• If a hydroxyl-bearing carbon has two carbon-containing substituents, it forms a ketone.
• A terminal –CH₂OH group forms methanal (formaldehyde).

The reaction is usually carried out using periodic acid (HIO₄) or a periodate salt such as sodium periodate (NaIO₄).

Examples

Mechanism

A commonly used simplified mechanism is as follows. ^[2]

Step 1: Formation of a Periodate Ester

One of the hydroxyl oxygen atoms of the vicinal diol bonds to the iodine atom of the periodate reagent, forming a periodate ester-type intermediate.

Because the second hydroxyl group is attached to the neighboring carbon, it is positioned close to the same iodine atom.

Step 2: Formation of a Cyclic Periodate Intermediate

The oxygen atom of the neighboring hydroxyl group also bonds to the same iodine atom. As a result, a cyclic periodate intermediate forms in which both diol oxygen atoms are attached to iodine.

This cyclic arrangement positions the carbon–carbon bond between the two original hydroxyl-bearing carbons for cleavage.

Step 3: Carbon–Carbon Bond Cleavage

The cyclic intermediate undergoes oxidative fragmentation. During this process, the carbon–carbon bond between the two original hydroxyl-bearing carbons breaks. At the same time, a carbonyl group forms at each carbon, and the periodate oxidant is reduced.

The final organic products are aldehydes, ketones, or a combination of both, depending on the original diol.