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.