Dakin Reaction & Oppenauer Oxidation

Session Objectives

By the end of this session, students will be able to:

• Dakin Reaction

• Mechanism of Dakin Reaction

• Oppenauer Oxidation

• Mechanism of Oppenauer Oxidation

Dakin Reaction

• Dakin reaction) is an organic redox reaction in which an ortho- or para-hydroxylated phenyl aldehyde (2-hydroxybenzaldehyde or 4-hydroxybenzaldehyde) or ketone reacts with hydrogen peroxide in base to form a benzenediol and a carboxylate.

• Overall, the carbonyl group is oxidized, and the hydrogen peroxide is reduced.

Reaction Mechanism of Dakin Reaction

• The Dakin reaction starts with nucleophilic addition of a hydroperoxide anion to the carbonyl carbon forming a tetrahedral intermediate.

• The intermediate collapses causing [1,2]-aryl migration, hydroxide elimination, and formation of a phenyl ester.

• The phenyl ester is subsequently hydrolyzed: nucleophilic addition of hydroxide from solution to the ester carbonyl carbon forms a second tetrahedral intermediate, which collapses, eliminating a phenoxide and forming a carboxylic acid.

• Finally, the phenoxide extracts the acidic hydrogen from the carboxylic acid, yielding the collected products

Dakin Reaction

Reaction Mechanism of Dakin Reaction

Synthetic applications of Dakin reaction

• The Dakin reaction is most commonly used to synthesize benzenediols and alkoxyphenols.

• Catechol, for example, is synthesized from o-hydroxy and o-alkoxy phenyl aldehydes and ketones, and is used as the starting material for synthesis of several compounds, including the catecholamines, catecholamine derivatives, and 4-tert-butylcatechol, a common antioxidant and polymerization inhibitor.

• Other synthetically useful products of the Dakin reaction include guaiacol (2-Methoxyphenol (a precursor of several flavorants; hydroquinone (benzene-1,4-diol or quinol) a common photograph-developing agent; and 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole, two antioxidants commonly used to preserve packaged food.

• In addition, the Dakin reaction is useful in the synthesis of indolequinones, naturally occurring compounds that exhibit high anti-biotic, anti-fungal, and anti-tumor activities.

Oppenauer Oxidation

• Oppenauer oxidation, named after Rupert Viktor Oppenauer,is a gentle method for selectively oxidizing secondary alcohols to ketones.

• Alcohols on refluxing with aluminium isopropoxide in acetone are oxidisied to aldehydes or ketones.

• Acetone acts as hydrogen acceptor and it is converted into isopropyl alcohol.

• The presence of excess of acetone drives the reaction towards the oxidation product.

Reaction Mechanism of Oppenauer Oxidation

Synthetic applications of Oppenauer Oxidation

• The Oppenauer oxidation is used to prepare analgesics in the pharmaceutical industry such as morphine and codeine.

• For instance, codeinone is prepared by the Oppenauer oxidation of codeine.

• The Oppenauer oxidation is also used to synthesize hormones.

• Progesterone is prepared by the Oppenauer oxidation of pregnenolone.

Summary

• Dakin oxidation (or Dakin reaction) is an organic redox reaction in which an ortho- or para-hydroxylated phenyl aldehyde (2-hydroxybenzaldehyde or 4-hydroxybenzaldehyde) or ketone reacts with hydrogen peroxide in base to form a benzenediol and a carboxylate.

• Overall, the carbonyl group is oxidized, and the hydrogen peroxide is reduced.

• Oppenauer oxidation, named after Rupert Viktor Oppenauer, is a gentle method for selectively oxidizing secondary alcohols to ketones.