reagents part of POC 3 SYLLABUS 4TH SEM

Oppenauer oxidation
•
 The Oppenauer oxidation is an organic reaction used to convert a primary
or secondary alcohol to a ketone using another excess ketone reagent
(such as acetone) and an aluminium triisopropoxide catalyst.
 The oxidation is highly selective for secondary alcohols and does not
oxidize other sensitive functional groups such as amines and sulphides
 The Oppenanuer oxidation is commonly used in various industrial
processes such as the synthesis of steroids, hormones, alkaloids, terpenes
, etc.

 Lithium aluminium hydride is widely used in organic chemistry as a
reducing agent
 It is more powerful than the related reagent sodium borohydride
owing to the weaker Al-H bond compared to the B-H bond.
 Often as a solution in diethyl ether or THF and followed by an acid
workup,
 it will convert esters, carboxylic acids, acyl chlorides, aldehydes,
and ketones into the corresponding alcohols .
 Similarly, converts amide, nitro, nitrile, imine, oxime,[23]
and azide
compounds into the amines
 It reduces quaternary ammonium cations into the corresponding
Lithium aluminium hydride

Step 1:
The nucleophilic H from the hydride reagent adds to the
electrophilic C in the polar carbonyl group of the ester. Electrons from
the C=O move to the electronegative O creating the tetrahedral
intermediate a metal alkoxide complex
Step 2:
The tetrahedral intermediate collapses and displaces the alcohol
portion of the ester as a leaving group, in the form of the
alkoxide, RO-
. This produces an aldehyde as an intermediate.
Step 3:
Now we are reducing an aldehyde.
The nucleophilic H from the hydride reagent adds to the electrophilic C in
the polar carbonyl group of the aldehyde. Electrons from the C=O move to
the electronegative O creating an intermediate metal alkoxide complex.
Step 4:
This is the work-up step, a simple acid/base reaction. Protonation of the
alkoxide oxygen creates the primary alcohol product from the intermediate
complex.
MECHANISM OF THE REACTION OF
LiAlH4 WITH AN ESTER

Step 1:
The nucleophilic H from the hydride reagent adds to the
electrophilic C in the polar carbonyl group of the ester. Electrons
from the C=O move to the electronegative O creating
the tetrahedral intermediate, a metal alkoxide complex
Step 2:
The tetrahedral intermediate collapses and displaces the O as part of a
metal alkoxide leaving group, this produces a highly reactive iminium
ion an intermediate.
Step 3:
Rapid reduction by the nucleophilic H from the hydride reagent as it
adds to the electrophilic C in the iminium system. π electrons from
the C=N move to the cationic N neutralising the charge creating the
amine product
MECHANISM OF THE REACTION OF
LiAlH4 WITH AN AMIDE

 Dakin Reaction is the replacement of the aldehyde group of ortho and para
hydroxy and ortho amino-benzaldehyde (or ketone) by a hydroxyl group on
reaction with alkaline hydrogen peroxide.
 The product formed depends on the starting material. If ortho substituted phenol
is the starting material, then cathchol is formed. In mechanism, para substituted
phenol is explained which results in the formation of quinol.
 The oxidation of aldehydes and ketones to the corresponding phenols is known as
Dakin reaction.
 The reaction works best if the aromatic aldehyde or ketone is electron rich.
DAKIN REACTION The reagents used in Dakin
reaction are; Alkaline H2O2,
Acidic H2O2,
Peroxybenzoic acid,
Peroxyacetic acid),
Sodium percarbonate,
Urea-H2O2 adduct

 Dakin Reaction Mechanism
The Dakin oxidation starts with nucleophilic addition of a hydroperoxide anion
to the carbonyl carbon, forming a tetrahedral intermediate (2).
 The intermediate collapses, causing [1,2]-aryl migration, hydroxide elimination,
and formation of a phenyl ester (3).
 The phenyl ester is subsequently hydrolyzed: nucleophilic addition of hydroxide
from solution to the ester carbonyl carbon forms a second tetrahedral
intermediate (4), which collapses, eliminating a phenoxide and forming a
carboxylic acid (5).
 Finally, the phenoxide extracts the acidic hydrogen from the carboxylic acid,
yielding the collected products (6).[1][2]
.

• The Dakin oxidation has two rate-limiting steps:
nucleophilic addition of hydroperoxide to the carbonyl
carbon and [1,2]-aryl migration
• Therefore, the overall rate of oxidation is dependent on
the nucleophilicity of hydroperoxide, the electrophilicity
of the carbonyl carbon, and the speed of [1,2]-aryl
migration.
• The alkyl substituents on the carbonyl carbon,
• the relative positions of the hydroxyl
• carbonyl groups on the aryl ring,
• the presence of other functional groups on the ring,
• the reaction mixture pH are four factors that affect these
rate-limiting steps
Factors affecting reaction kinetics

 Variations in the aryl rings' migratory aptitudes can be explained by this. Hydroxyl
groups ortho or para to the carbonyl group concentrate electron density at the aryl
carbon bonded to the carbonyl carbon (10c, 11d).
 Phenyl groups have low migratory aptitude, but higher electron density at the
migrating carbon increases migratory aptitude, facilitating [1,2]-aryl migration and
allowing the reaction to continue.
 M-hydroxy compounds do not concentrate electron density at the migrating
carbon (12a, 12b, 12c, 12d); their aryl groups' migratory aptitude remains low.
The benzylic hydrogen, which has the highest migratory aptitude, migrates instead
(8), forming a phenyl carboxylic acid
 Substitution of phenyl hydrogens with electron-donating groups ortho or para to
the carbonyl group increases electron density at the migrating carbon, promotes
[1,2]-aryl migration, and accelerates oxidation.
 Substitution with electron-donating groups meta to the carbonyl group does not
change electron density at the migrating carbon; because unsubstituted phenyl
group migratory aptitude is low, hydrogen migration dominates.

Concentration of electron density at the migrating carbon with para (top) and ortho
(bottom) hydroxyl group
Concentration of positive charge at migrating carbon with para nitro group
 Substitution with electron-withdrawing groups ortho or para to the carbonyl
decreases electron density at the migrating carbon (13c), inhibits [1,2]-aryl
migration, and favors hydrogen migration

1. The Dakin oxidation is most commonly used to synthesize
benzenediols[7]
and alkoxyphenols.
2. 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,[9]
catecholamine derivatives, and 4-tert
-butylcatechol, a common antioxidant and polymerization
inhibitor.
3. Other synthetically useful products of the Dakin oxidation
include guaiacol, a precursor of several flavorants;
4. hydroquinone, a common photograph-developing agent;
5. 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-
hydroxyanisole, two antioxidants commonly used to preserve
packaged food.
6. In addition, the Dakin oxidation is useful in the synthesis of
indolequinones, naturally occurring compounds that exhibit
high anti-biotic, anti-fungal, and anti-tumor activities

1. Carbocation is formed in the presence of organic solvent.
2. Carbanion is formed when electrons starts flowing from zinc to
carbonyl carbon.
3. Hydrogen gets added to the carbon during protonation.
4. By the similar way, the second hydrogen also gets added to carbon, so
that, alkane is formed from carbonyl compound

APPLICATIONS
• This reaction has widely used to convert a carbonyl group into a
methylene group.
• Also important application in the preparation of polycyclic aromatics
and aromatics containing unbranched side hydrocarbon chains.
• To reduce aliphatic and mixed aliphatic-aromatic carbonyl compounds
• Reduction of keto acids, acids with a- and b-keto acids are generally
not reduced by Clemmensen reduction.

WOLFF–KISHNER REACTION
 The Wolff– Kishner reduction was discovered independently by
N. Kishner in 1911 and L. Wolff in 1912.
 The Wolff– Kishner reduction is a reaction used in organic
chemistry to convert carbonyl functionalities into methylene
groups.
 The Wolff-Kishner reduction is an organic reaction used to
convert an aldehyde or ketone to an alkane using hydrazine,
base, and thermal conditions.
 Because the Wolff–Kishner reduction requires highly basic
conditions, it is unsuitable for base-sensitive substrates.

BIRCH REDUCTION
The reaction was reported in 1944 by the Australian chemist Arthur Birch
(1915–1995) working in the Dyson Perrins Laboratory at the University of
Oxford
Birch Reduction converts aromatic compounds having a benzenoid ring into a
product, 1,4-cyclohexadienes, in which two hydrogen atoms have been
attached on opposite ends of the molecule.
Birch Reduction is the organic reduction of aromatic rings in liquid ammonia
with sodium, lithium or potassium and an alcohol, such as ethanol and tert-
butanol.

Basic reaction mechanism
The first step of the mechanism of the Birch reduction is a one-electron transfer into an
antibonding π orbital of the aromatic system.
The resulting product is a radical anion, which is then protonated by ethanol, yielding a
cyclohexadienyl radical.
This resonance-stabilized allyl radical is converted into a cyclohexadienyl anion by an
additional one-electron transfer.
Subsequently, the cyclohexadienyl anion is also protonated by ethanol.
Surprisingly, the final protonation exclusively yields the 1,4-cyclohexadiene and not the
thermodynamically more stable, conjugated 1,3-cyclohexadiene.

In substituted aromatic compounds, the substituents control the position of the 1,4-double
bonds:
Electron-donating substituents, such as alkoxy or alkyl groups, are located at one of the
double bonds of the product.
Electron-withdrawing substituents, like carboxyl or amide groups, for instance, are
located at one of the sp3-hybridized carbons in the ring of the product.

The most common reaction mechanism of the Beckmann rearrangement consists
generally of an alkyl migration anti-periplanar to the expulsion of a leaving group
to form a nitrilium ion. This is followed by solvolysis to an imidate and then
tautomerization to the amide
nitrilium ion

Stereochemistry
The migrating group is always approaching the nitrogen atom on the side opposite to the
oxygen atom; this rearrangement is highly stereospecific that is the group anti to the
oxime hydroxyl group always migrates regardless of relative migratory aptitude of the
two groups. Thus, different geometrical isomers of oximes sometimes give isomeric
amides by the Beckmann rearrangement.
Eg
- In acetophenone oxime with the stereochemistry shown below it is phenyl group which
migrates and thus the product formed is acetanilide.

Claisen Schmidt
‐
condensation
•The reactions between a ketone and a carbonyl compound
lacking an alpha Hydrogen(Cross Aldol condensation) is called
‐
Claisen Schmidt condensation.
‐
•These reactions are named after two of its pioneering
investigators Rainer Ludwig Claisen and J. G. Schmidt, who
independently published on this topic in 1880 and 1881. An
example is the synthesis of dibenzylideneacetone.

MECHANISM:
•The first part of this reaction is
an aldol reaction, the second
part a dehydration—an
elimination reaction.
•Dehydration may be
accompanied by decarboxylation
when an activated carboxyl
group is present.
• The aldol addition product can
be dehydrated via two
mechanisms; a strong base like
potassium t butoxide, potassium
‐
hydroxide or sodium hydride in
an enolate mechanism, or in an
acid catalyzed enol mechanism
‐ .

Used in synthesis of Chalcones

The Schmidt
reaction
• Schmidt Reaction involves the reaction between the carboxylic acids and hydrazoic acid in the
presence of sulfuric acid to form amines. This reaction was discovered by Karl Friedrich
Schmidt in 1924.
• The catalyst used in this reaction is usually sulfuric acid.
• Protic acid and Lewis acid can also be used.
• Azides are nucleophilic at their terminal nitrogen atoms, and may add to suitably activated
electrophiles in the presence of a Brønsted or Lewis acid.
• Upon addition, the newly bound nitrogen atom becomes electron-deficient and is subject to 1,2-
migration of a carbon or hydrogen substituent with loss of a molecule of dinitrogen.
• Related reactions of alkyl azides may yield substituted amides, lactams, or amines

•Schmidt Reaction Mechanism
• Initially, protonation reaction
takes place and water molecule is
lost forming acylium ion.
• The acylium ion formed then
reacts with hydrazoic acid forming
protonated azido ketone.
• The alkyl group migrates from
carbon atom to nitrogen atom by
rearrangement reaction with loss
of nitrogen gas to form protonated
isocyanate ion.
• The protonated isocyanate is
attacked by water forming
carbamate 4.
• After deprotonation loses carbon
dioxide to the amine

reagents part of POC 3 SYLLABUS 4TH SEM

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