OXIDATION AND REDUCTION

OXIDATION REDUCTION
1- Addition of oxygen 1- Loss of oxygen
2- Loss of hydrogen 2- Addition of hydrogen
3- Loss of electron 3- Addition of electron
4- Increase in oxidation number is oxidation 4- Decrease in oxidation number is reduction

Oxidation and reduction are reverse of each other and always proceed simultaneously. Oxidation
and Reduction are important reactions in organic chemistry for converting one functional group
into other, eg:
oxi oxi Aldehyde oxi oxi
Alkane red Alcohol red / Ketone red Carboxylic red
CO2 + H2O
acid

Redox Reactions: Reactions in which oxidation and reduction takes place simultaneously are
also called redox reactions (red = reduction, ox = for oxidation).

Some important oxidizing agents:

Cu/O2
KMnO4/H2SO4 or KOH
Perchloric acid (HClO4) and Periodic acid (HIO4)
Ag + O2
O3 (Ozone)
Pb(CH3COO)4 + CH3COOH
CrO3/FeO/Fe2O3/OsO4
Al2O3
SeO2 (Selenium dioxide)
H2SeO3 (Selenous acid)
Peracids (Perbenzoic acid, peracetic acid. They contain one extra oxygen atom than
normal carboxylic acid)

1|Page
 Pyridinium chlorochromate (PCC), [C5H5NH]+[CrO3Cl]− (in CH2Cl2)
CrO3/ H2SO4 (Jones Reagent)

Pyridinium Dichromate (PDC)

Some important reducing agents:

LiAlH4 (Lithium aluminium hydride is Excellent reducing agent)
NaBH4 (Sodium boro hydride)
Zn/Hg + HCl (Zn/Hg is called zinc amalgam) (Used in Clemmensen reduction)
NH2NH2 / KOH (Used in Wolf-Kishner Reduction)
Pt/H2 or Pd/ H2 (Very efficient reducing agent but expensive)
Ni/ H2 (Raney Nickel)
Pd + C + H2
PdCl2
Pd + CaCO3
Na/ Liquid NH3 (Birch reduction)

Some important organic radicals:

Radical are species (atoms, ions molecules) with one or more unpaired electrons.
.
R Alkyl radical
.

Phenyl radical

.CH2

Benzyl radical

2|Page
Oxidation of Alkanes
Alkanes are very stable compounds. It is very difficult to oxidize them. Usually alkanes
undergo combustion and produces carbon dioxide water and heat.

Oxidation of Alkenes
Alkenes undergo oxidation and produces variety of compounds like diols, aldehydes,
ketones, carboxylic acid, etc.

3|Page
1- Oxidation of Alkenes with OsO4
Alkenes first react with osmium tetraoxide to produce osmate ester which on hydrolysis
gives cis-diols.
H
H H H OH

+ OsO4 2H2O + H2OsO4

H H H OH
H
cis diol

Mechanism (Example 1)

4|Page
H H H H O
O O H O O H O

+ +VIII H2O Os +VII

Os Os+VI

H H O O O O H O O
H +
H H O
H H
Osmate Ester

H H
+
O
H H O H O
H O O H O H O
H2O Os +VI
Os +VII Os +VI
-
H OH O H OH O H O O
+
H O H O H O
H H
H H

H H
+
O
H - H
H O O H OH HO O

+ Os +VI + Os +VI (H 2OsO4)

OH H OH HO
H O O
H O H
H
cis diol

Mechanism (Example 2)

5|Page
H3C H H H
O O H3C O O H3C O O

+ + H2O Os +VII
Os VIII Os +VI

H3C H O O O O H3C O O
H3C +
H H O
2-Butene H H
Osmate Ester

H H
+
O
H O H O H O
H3C O H3C O H3C O
H2O
Os +VII Os +VI Os +VI
-
H3C OH O H3C OH O H3C O O
H H O H +
O O
H H
H H

H H
+
O
H - H
H3C O H3C OH HO O
O

+ Os +VI + Os +VI (H 2OsO4)

OH H3C OH HO O
H3C O
H H
O
H 2,3 -Butanediol
cis diol

2- Oxidation of Alkenes with KMnO4

Reaction of alkenes with cold alkaline KMnO4 produces cis-diols.

6|Page
 H
H H H OH

+ KMnO 4 2H2O + H2MnO 4

H H H OH
H
cis diol

Mechanism (Example 1)
H H - H - H -
O O H O O H O O

+ H2O Mn. +VI

Mn.+VII Mn+V
.

H H O O O O H O O
H
H H +
O
H H
Cyclic Manganese Ester

H H
+
O
H - H H
H O O H O - H -
O O O
Mn. +VI H2O
Mn. +V Mn. +V

OH O O - O
H H OH H O
H +
O H O H O
H H H
H

H H
+
O H
-
H - HO O
H O - H OH
O
+ Mn. +V + Mn+V
.

OH O OH HO O
H H
H O H
H
cis diol 1,2 -Ethanediol/Glycol

Note: In the presence of acid the C = C is cleaved or broken and carbonyl compounds are
produced.

3- Oxidation of Alkene with CrO3

7|Page
 OH
H H
H OH
+ CrO 3 H2O
Cis - diol
H OH
H H
H

Mechanism
H

H :O : OH
O H
H H O
H H O H
+ Cr O Cr O H
H O H
+ H2CrO3

H O
H H
O H :O : H

Mechanism of this reaction is same as for reaction of Alkene with OsO4 and KMnO4.

4-Oxidation of Alkene by Ozonolysis

In ozonolysis bond between carbon atoms is cleaved and two carbonyl compounds are
obtained.

8|Page
 H H

. .

H H
H H - H H
O
Zn/H 2O
+ O
+ CH3COOH O + O + H2O 2
H H O H H

Mechanism (Example 1)
H
H H - H H
O O
-
+ O
+ O O + + O
O H O
H H O H H
H H

O O O O O O
H H H H Zn/H 2O H H
+
+ CH3COOH O
H O H H O H H H

H H

H2O

H H
+ H
O O O O + O O
H H -H
H H O + H
H O H H O H O
H H
+
H O H O H H
H H

H H

O + O + H2O 2

H H

Mechanism (Example 2)

9|Page
 H
H3C H - H3C H
O O . -
+ O
+ .
O O + + O
O H O
H3C H O H H3C
H CH3

O O O O O O
H H H H Zn/H 2O H H
+
+ CH3COOH O
H3C O CH3 H3C O CH3 H3C CH3

H H

H2O

H H
+ H
O O O O + O O
H H -H
H H O + H
H3C O CH3 H3C O CH3 O
H3C CH3
+
H O H O H H
H H

H H

O + O + H2O 2

H3C H3C

5- Woodward Hydroxylation of Alkene (Cis-diol)

10 | P a g e
 H H H H
I 2, AgOAc
+ H H
H2O, H
H H HO OH
+
Ag

+
I I
H H H H - H H
I -- I CH3COO

H H H H H H
Cyclic Iodonium ion O
O

CH3

+
-Ag I

H H
H H H H
H H
H H H H

H2 O Delocalization
+
+ O O +
O O H O O

CH3
H3C OH H3C

H H H H

H H H H O

Hydrolysis H3C C O H
+
H2 O OH
O OH HO

Monoacylated diol
CH3

6- Synthesis of Trans-diols. Oxidation of Alkenes (Prevost Reaction).

11 | P a g e
Mechanism
CH3
H3C CH3 +I
-
H3C CH3
H3C
I+-- I- -
CH3 COO Ag
+
+ O CH3
- I
-I -AgI O
H3C CH3 H3C I
H3C
CH3 CH3

Iododium ion
-I-

CH3 H3C CH3 CH3

HO CH3 + - O
H ---- OH O CH3 O -
CH3 COO Ag
+ CH3
H3C +
H3C OH + -
O H3C O -AgI CH3
H ---- OH O
CH3 CH3 CH3 CH3

+ 2 H3C OH

12 | P a g e
 CH3
- CH3
H3C CH3 H3C +I H3C
+ -
I -- I -
CH3COO Ag
+
I
+ O CH3
-
-I -AgI O H3C
H3C CH3 H3C
I
CH3 CH3

Iododium ion
-
-I

CH3 H3C CH3 CH3

HO CH3 O CH3 - + O
H - OH O CH3COO Ag CH3
O HC H3C +
H3C OH H - OH 3 O -AgI CH3
O
CH3 CH3 CH3 CH3
O
Diester

+ 2 H3C OH

7- Epoxidation
In this mechanism oxygen atom from per acid is transferred to C = C resulting in the formation
of three membered ring called epoxide and the process is called epoxidation.
Following peroxy acids can be used for epoxidation.
O
O O O Cl OH
O
C O C O C O
H O H H O H F 3C O H

Performic acid Peracetic acid Trifluoroperacetic acid m-Chloroperbenzoic acid

Example 1
O
O O
H3C CH3
H3C CH3
+ C O
+ C
H3C CH3 F 3C O H F 3C O H
H3C CH3

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Mechanism
With Trifluoroacetic acid
H
H3C CH3 O O : O:
+ C O C + H3C + CH3
H3C CH3 F 3C O H F 3C
-
O
H3C CH3

H
O O +
O O
H3C CH3
C
+ C -
+ H3C CH3
F 3C O
F 3C O H H3C CH3 H3C CH3

Mechanism
With Peracetic acid
H
H3C CH3 O O : O:
+ C O C + H3C + CH3
H3C CH3 H3C O H H3C
-
O
H3C CH3

H
O O +
O O
H3C CH3
C
+ C -
+ H3C CH3
H3C O
H3C O H H3C CH3 H3C CH3

14 | P a g e
Oxidation of Alcohols
Oxidation of alcohols involve removal of two hydrogen atoms one from hydroxyl group
(OH) and second hydrogen from alpha carbon.

 CH3
H3C
   
CH2 CH OH 
CH2 H3C C OH
H3C CH2 OH
 H3C
 CH3

Primary Alcohol Secondary Alcohol Tertiary Alcohol

Primary alcohols are oxidized into aldehydes while secondary alcohols are oxidized into ketones.
Tertiary alcohols cannot be oxidized due to absence of alpha H. On further oxidation aldehydes
and ketones are changed into carboxylic acid. Hydrogen attached with alpha carbon is called
alpha hydrogen and hydrogen attached with beta carbon is called beta hydrogen.

15 | P a g e
1- Swern Oxidation

The Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or
secondary alcohol is oxidized to an aldehyde or ketone using oxalyl chloride, dimethyl
sulfoxide (DMSO) and an organic base, such as triethylamine (Et3N:). It is one of the many
oxidation reactions commonly referred to as 'activated DMSO' oxidations. The reaction is known
for its mild character and wide tolerance of functional groups.

The by-products are dimethyl sulfide (Me2S), carbon monoxide (CO), carbon dioxide (CO2)
and—when triethylamine is used as base—triethylammonium chloride (Et3NHCl). Of the
volatile by-products, dimethyl sulfide has a strong, pervasive odour and carbon monoxide is
acutely toxic, so the reaction and the work-up needs to be performed in a fuming hood. Dimethyl
sulfide is a volatile liquid (B.P. 37 °C) with an unpleasant odour at high concentrations.

Mechanism

The first step of the Swern oxidation is the low-temperature reaction of DMSO, 1a, formally
as resonance contributor 1b, with oxalyl chloride, 2. The first intermediate, 3, quickly
decomposes giving off carbon dioxide and carbon monoxide and producing
chloro(dimethyl)sulfonium chloride, 4.

After addition of the alcohol 5, the chloro(dimethyl)sulfonium chloride 4 reacts with the alcohol
to give the key alkoxysulfonium ion intermediate, 6. The addition of at least 2 equivalents of
base — typically triethylamine — will deprotonate the alkoxysulfonium ion to give the
sulfur ylide 7. In a five-membered ring transition state, the sulfur ylide 7 decomposes to give
dimethyl sulfide and the desired carbonyl compound 8.

16 | P a g e
 .. .. .. .. .. -
:O: : Cl : : O-: : Cl : :O : Cl : Cl
:O : H3C
..
S
.. CH
+ H3C
..
H3C
..
+
: S Cl :
..
H3C 3 : Cl : :O : :S
+
O :O : :S
+
O :O : H3C
.. .. : Cl : .. 4
H3C .. H3C
1 2 .. -
Dimethyl sulfoxide Oxalyl chloride 3a : Cl : + CO 2 + CO
..
3b

Et 3 N:
H
H3C ..+ CH3 H3C ..+ C H
H H3C H S H S H
.. .. -HCL .. ..
+ -
R C O H
.. + :S Cl :
..
R C O Cl R C O
.. Cl
-

H H3C - H H
Cl 6b
5 4
6
+ -
-Et 3 N H.Cl

H H CH3
H3C
 .. ..
-78 C
O + S R C O
..
S
H CH2
R H3C

8 Dimethyl sulphide 7

Original publication: Tetrahedron, 1978, 34, 1651. Tetrahedron: Asymmetry, 2007, 18, 2021.

17 | P a g e
2- Dess-Martin Periodinane Oxidation of Alcohol

Dess–Martin periodinane (DMP) is a chemical reagent used to oxidize primary

alcohols to aldehydes and secondary alcohols to ketones. This periodinane has several
advantages over chromium- and DMSO-based oxidants that include milder conditions (room
temperature, neutral pH), shorter reaction times, higher yields, simplified workups, high
chemoselectivity, tolerance of sensitive functional groups, and a long shelf life. However, use on
an industrial scale is made difficult by its cost and its potentially explosive nature. It is named
after the American chemists Daniel Benjamin Dess and James Cullen Martin who developed the
reagent in 1983. It is based on IBX, but due to the acetate groups attached to the central iodine
atom, DMP is much more reactive than IBX and is much more soluble in organic solvents.

O
CH3
O CH3
O
O
O O Dess - Martin Periodinane (DMP)
I
O H C
3

OAc
AcO
OAc
I
O

OH O
O
DMP C
CH
R R R R

O
-
AcO = H3C C O

Mechanism
O O
CH3 CH3 CH3
O CH3 O O
CH3
O O
O O O
O O O O
I I CH2 I
H3C CH2 O H Slow
H3C -CH3COOH
O
CH3 -CH3COOH
O + H3C H

O O O

18 | P a g e
 O
CH3 CH3 CH3
O R
CH3 HO R O O
O O HC R
O O O
O O O CH
I HO R Slow HO
I R - I
CH3COO
H3C
-2CH3COOH
O
-CH3COOH
O +
O

O O O R

Schreiber and coworkers have shown that water increases the rate of the oxidation reaction. Dess
and Martin had originally observed that the oxidation of ethanol was increased when there was
an extra equivalent of ethanol. It is believed that the rate of dissociation of the final acetate
ligand from the iodine is increased, because of the electron-donating ability of the hydroxyl
group (thus weakening the I-OAc bond).

O O
CH3 CH3 CH3
O CH3 O O
CH3
O O
O O O
O O O O
I I CH2 I
H3C CH2 O H Fast
H3C -CH3COOH
O
CH3 -CH3COOH
O + H3C H

H2O Solvent
O O O

19 | P a g e
3- Oppenauer Oxidation

Is named after chemist Rupert Viktor Oppenauer. It is a gentle method for

selective oxidation of secondary alcohols to ketones.

Al(i-PrO) 3 / Heat
OH O OH O
Oppenauer Oxidation
CH + CH +
R1 R2 H3C CH3 Meerwein-Ponndorf-Verley Reduction R1 R2 H3C CH3

H3C CH3
CH
H3C O
i-PrO CH O . Al(i-PrO) 3

H3C Al

O O
H3C CH3
HC CH

CH3 H3C

The reaction is the opposite of Meerwein–Ponndorf–Verley reduction. The alcohol is

oxidized with aluminium isopropoxide in excess acetone. This shifts the equilibrium toward the
product side.

The oxidation is highly selective for secondary alcohols and does not oxidize other sensitive
functional groups such as amines and sulfides. Though primary alcohols can be oxidized under
Oppenauer conditions, primary alcohols are seldom oxidized by this method due to the
competing aldol condensation of aldehyde products. The Oppenauer oxidation is still used for the
oxidation of acid labile substrates. The method has been largely displaced by oxidation methods
based on chromates (e.g. pyridinium chlorochromate) or dimethyl sulfoxide (e.g. Swern
oxidation) or Dess–Martin oxidation due to its use of relatively mild and non-toxic reagents (e.g.
the reaction is run in acetone/benzene mixtures). The Oppenauer oxidation is commonly used in
various industrial processes such as the synthesis of steroids, hormones, alkaloids, terpenes, etc.

20 | P a g e
Mechanism

Al Oi-Pr
Oi-Pr Al Oi-Pr
+ Oi-Pr
.. Al Oi-Pr O Oi-Pr
H O + i PrOH
OH 2
Oi-Pr CH 6
R1 R2 CH 5
CH
R1 R2 R1 R2
- ..
3 : Oi-Pr ..
1 .. O
4
C
H3C CH3
7

Al (O-iPr) 2
O-iPr O-iPr O-iPr
O O
Al CH3 Al
O-iPr
CH + C O O ......... R1
CH3 C O
H3C R1 R2
R1 H3C O
H3C H
10 9 R2 H R2
CH3
Transitory 6 membered chair form
8

Al (O-iPr) 2
O HO
H2O
CH Al (O-iPr) 2
CH
H3C CH3 H3C CH3 OH
10 11 12

In the first step of this mechanism, the alcohol (1) coordinates to the aluminium to form a
complex (3), which then, in the second step, gets deprotonated by an alkoxide ion (4) to
generate an alkoxide intermediate (5). In the third step, both the oxidant acetone (7) and
the substrate alcohol are bound to the aluminum. The acetone is coordinated to the aluminum
which activates it for the hydride transfer from the alkoxide. The aluminum-catalyzed
hydride shift from the α-carbon of the alcohol to the carbonyl carbon of acetone proceeds
over a six-membered transition state (8). The desired ketone (9) is formed after the hydride
transfer.

21 | P a g e
 Advantages

An advantage of the Oppenauer oxidation is its use of relatively inexpensive and non-toxic
reagents. Reaction conditions are mild and gentle since the substrates are generally heated in
acetone/benzene mixtures. Another advantage of the Oppenauer oxidation which makes it
unique to other oxidation methods such as pyridinium chlorochromate (PCC) and Dess–
Martin periodinane is that secondary alcohols are oxidized much faster than primary
alcohols, thus chemoselectivity can be achieved. Furthermore, there is no over oxidation
of aldehydes to carboxylic acids as opposed to another oxidation methods such the Jones
oxidation.

Modifications

1- Wettstein-Oppenauer reaction.

2- Woodward modification

22 | P a g e
4-Corey - Kim Oxidation
Dimethyl sulfide (Me2S) is treated with N-chlorosuccinimide (NCS), resulting in formation of an
"active DMSO" species that is used for the activation of the alcohol. Addition of triethylamine to
the activated alcohol leads to its oxidation to aldehyde or ketone and generation of dimethyl
sulfide. In variance with other alcohol oxidation using "activated DMSO," the reactive oxidizing
species is not generated by reaction of DMSO with an electrophile. Rather, it is formed by
oxidation of dimethyl sulfide with an oxidant (NCS).
H
O O
NCS. (CH3)2S
CH
Et3N:
R2 R1 R2
R1

Mechanism
O O O
CH3 H3C CH3 Cl-
N Cl + :S -
N + S
+
Cl N
+
S
CH3 H3C CH3
O O O
H
:O

CH
H R1 R2

- CH2
CH2 -
- + Cl O
+ Cl S
O S O CH3
-Et3N.HCl Et3N:
O
(CH3)2S + CH3
-Succinimide CH + NH
R1 R2 H C
R1 R2
R1 R2 O

Under Corey–Kim conditions allylic and benzylic alcohols have a tendency to evolve to the
corresponding allyl and benzyl chlorides unless the alcohol activation is very quickly followed
by addition of triethylamine. In fact, Corey-Kim conditions - with no addition of triethylamine-
are very efficient for the transformation of allylic and benzylic alcohols to chlorides in presence
of other alcohols.

23 | P a g e
5- Jones Oxidation of Alcohols

For Primary Alcohols

CrO3 O CrO3 O
H3C Aq-H2SO4 H3C Aq-H2SO4 H3C
OH H Acetone OH
Acetone
1-Propanol 1-Propanal Propanoic Acid

For Secondary Alcohol

OH CrO3 O
Aq-H2SO4
H3C CH3 H3C CH3
Acetone
2-Propanol Propanone

In case of secondary alcohols oxidation leads to ketones, as ketones are difficult to oxidize so no
further oxidation to carboxylic acid occurs.

Tertiary Alcohols donot undergo oxidation as they lack alpha hydrogen on alpha carbon.

Mechanism

First step involves reaction between CrO3 and H2SO4 or Na2Cr2O7 with H2SO4 to produce
chromic acid H2CrO4 which is active oxidizing specie.

O O O O
H2SO4 H2SO4
HO Cr OH 1/2 HO Cr O Cr OH 1/2 Na 2Cr2O7
Cr
H2 O H2O
O O O
O O

24 | P a g e
Mechanism of Oxidation of Primary Alcohols

HO O OH

.. O Cr
: OH +
O -
H3C CH2 + HO Cr OH
H3C CH2
O
H
O

.. -2H2O
+H 2O:

O
O O
H2O
H2O + HO Cr + H3C C H
H3C CH O Cr OH

O H O

Mechanism of Oxidation of Secondary Alcohols

.. O -
H O: O H O
R1 H O H
+ Cr
H O
+
Cr
R1 R2 O H
H O R2 O H
O

- -
O O
R1 H O H R1
..
:O +
H H + H O Cr H O Cr O H
R2 O H R2
O O

-
O O O
R1
..
:O
H H
+ H O Cr O H
+ Cr + H2O
R2 R1 R2 HO OH
O

25 | P a g e
6 -Oxidation of Diols with Lead tetra acetate (Criegee Oxidation)
The Criegee oxidation is a glycol cleavage reaction in which vicinal diols are oxidized to
form ketones and aldehydes using lead tetra-acetate. It is analogous to the Malaprade reaction,
but uses a milder oxidant. This oxidation was discovered by Rudolf Criegee and coworkers and
first reported in 1931 using ethylene glycol as the substrate.
In this example lead tetra-acetate is used cleave a carbon-carbon bond in a vicinal diol (glycol).
This reaction is useful in the formation of ketones and aldehydes and involves a favourable five-
membered cyclic intermediate.

O O

H3C C O O C CH3

Pb
H3C C O O C CH3

O O

AcO OAc AcO OAc

Pb Pb

HO OH O O O O
Pb(CH 3COO) 4
H H H H H H
-2CH 3COOH
H H H H H H

-Pb(CH 3COO) 2

O O

H H
+ H H

26 | P a g e
7-Oxidation of Alcohols using periodic acid
Or Oxidative Cleavage of Vicinal Diols with Periodic Acid:
In this reaction, an intermediate cyclic ester is formed between periodic acid and the glycol
derivative and water is eliminated concurrently. Presumably, the ester dissociates via an aromatic
6-electron-5-center transition state into two carbonyl fragments and iodic acid. Iodine is reduced
from +VII to +V.

+ -
HIO 4 H + IO4

R1 OH O
CH O O
+VII
+ O I O
-
R1 C H + R2 C H +
+V
IO3
-
CH
R2 OH O

Lead tetra-acetate reacts analogously (similar manner). Unlike the periodic acid oxidation, the
reaction with lead tetra-acetate also takes place in non-aqueous media. The reaction proceeds via
a five-membered lead alkoxy intermediate similar to the one observed in the periodic acid
oxidation.

27 | P a g e
Mechanism
H H O H O
R1 : O: O O R1 : O: O R1 : O: O
CH CH CH
I +VII
+ I +VII I +VII

CH CH CH
-
R2 :O: O O R2 :O
+
O
-
R2 :O: O
-
-
H H O HO

..

H O
-
OH OH +
R1 :O
R1 O O R1 O O
CH
CH CH +
I +VII
I +VII I +VII
CH
CH CH
- - R2 O
R2 O O R2 O O
HO
O OH
H

-H 2 O

R1 O O O O
CH +VII +V
I O
-
R1 C H + R2 C H + HIO 3
CH
R2 O O

28 | P a g e
9- Oxidation of Alcohol with KMnO4

H2CrO4 Oxidation occurs in acid, KMnO4 oxidation occurs in the presence of base.

In KMnO4 oxidation, the Mn ester itself extracts the H+ from the alcohol carbon, while
in H2CrO4 oxidation the nucleophile is the solvent.

Mechanism
- + -
O O K O O
ionization +
Mn K + Mn

O O O O

Purple colour in solution

- O
H H O O
H H
C Mn C
-
Mn O
R O + O
+
O O R
H - O
H O

O O
H H H
-
OH -
Mn O
-
+ C
O - H OH
C Mn O
R R O O
O
O O
H H
-
(HMnO 4 )

29 | P a g e
10- Pfitzner-Moffatt oxidation

The oxidation of alcohols using the combination of DCC+Brønsted acid+DMSO is known as

the Pfitzner-Moffatt oxidation. The active species of this reaction is bulkier than those of the
Swern and the Parikh-Doering reactions. That this reaction can be carried out at room
temperature is another important merit.

Mechanism

Cy = Cyclohexyl = C 6H11

Cy H
Cy N:
H Cy H
N: + O
+ N
N C
C
+ C + H3C
S
CH3 :N
-Pyridine O
:N Cy
Cy :N +
Cy S
H3C CH3

H3C H OH

Cy H Cy H
N N: N:
H
H H3C C
H C
H H3C H O+
H3C O S O + S O :N
N
H3C H Cy H H H3C Cy
H

Cy H
N:
-
+ O C
N
H N:
H Cy

H
H
C CH3
H H
H3C H3C :S:
O S
+
H CH3 O CH3

30 | P a g e
The oxidation of primary and secondary alcohols to the corresponding aldehydes and ketones
can be carried out under mild and almost neutral conditions.

Original publication: J. of American Chem. Soc., 1963, 85, 3027.

Oxidation of Carbonyl Compounds

1- Oxidation of Aldehyde / Silver Mirror Test / Tollen’s Test
Here are the two half reactions:
Reduction half reaction
[Ag(NH3)2]+ + e− ⟶ Ago + 2NH3
Oxidation half reaction
RCHO + 3OH- ⟶ RCO2- + 2H2O + 2e-
Which together yield the overall reaction
2[Ag(NH3)2]+ + RCHO + 3OH− ⟶ 2Ago + RCO2− + 4NH3 + 2H2O
Here is a diagram of the reaction mechanism. The carbonyl group is oxidized in the process and
the Ag+ is reduced. The resultant oxidized aldehyde (now a radical cation) reacts with hydroxide
to form a tetrahedral intermediate. A gem-diol like intermediate is formed via a hydrogen shift,
which then continues on to the final carboxylate anion.

31 | P a g e
Mechanism

O O
. O. HO O.
. - -
. -e + OH
. .
.
R H R H R H
+ o R H
Ag Ag

- - OH
O O O
- -
-e OH
+ .
R OH -H 2O R OH
R OH R OH
o +
Ag Ag

-
-H 2O OH

-
R O

32 | P a g e
2- Oxidation of Aldehyde with H2CrO4

H H
+ O
O O
+ +H 2O
H3C + H H3C H3C
H
H H +
O
H H

+
-H

HO
HO OH
H OH H
Cr
Cr H
+
O O O O O
O
- H3C
H3C O H3C
H H H
OH OH OH

-H 2O +H 2O

HO
OH
O
Cr -H 3CrO4
O H3C
O OH
-
H3C O
H
OH

3- Baeyer Villiger Oxidation

The Baeyer–Villiger oxidation is an organic reaction that forms an ester from
a ketone or a lactone from a cyclic ketone, using peroxyacids or peroxides as the oxidant. The
reaction is named after Adolf von Baeyer and Victor Villiger who first reported the reaction in
1899.

33 | P a g e
Mechanism

In the first step of the reaction mechanism, the peroxyacid protonates the oxygen of the carbonyl
group. This makes the carbonyl group more susceptible to be attacked by the peroxyacid. Next,
the peroxyacid attacks the carbon of the carbonyl group forming what is known as the Criegee
intermediate. Through a concerted mechanism, one of the substituents on the ketone migrates to
the oxygen of the peroxide group while a carboxylic acid leaves. This migration step is thought
to be the rate determining step. Finally, de-protonation of the oxo-carbenium ion produces
the ester.

H
H O
O +
O
R1 R2
H O R3 R3
+ O + O
- O
O
R1 R2 R1 R2
O O O R3

H
H O
O +
O
+ HO R3
-H R1 R2
R1 O R2 R1 + O
O R2 O
O R3

+
O H

34 | P a g e
4- Fehling Solution Test

Fehling Solution
H O

O C C O -K+
CuSO4.5H 2O + 2NaOH + KNaC4H 4O6.4H2O Cu + Na2SO4 + 11H2O
Cupric sulfate Sod. hydroxide Pot. sod. tartrate - +
O C C OK

H O
Fehling Solution

Overall Reaction
O O

H3C C H + 2Cu2+ + 5 OH
-
H3C C O
-
+ Cu2O + 3H2O

Carboxylate Cuprous oxidered ppt

Mechanism of Fehling Solution Test

O O- O-
Cu2+ O
C R C 2+ C +
H -H 2O Cu C Cu
H H H
C C C C
- H H H H
.. R R H
:OH R
..

-
HO

-
O O -
- O
O +
C OH H C OH OH Cu
-Cu+ C
H C OH H
.C C
H C R Cu
+
Cu
2+
+ H
C H R
H R
H R

35 | P a g e
5- Benedict’s Solution Test
-
H O O O

+ Cu(citrate) 22- + Cu2O (s)

R R

Aldehyde/Aldose Benedict's reagent Carboxylate anion Brick -red ppt

(blue solution)

CuSO4.5H2O + Na2CO3 + Na3C6H5O7 --------------- Benedict’s Solution

CuSO4 + RCHO --------------- RCOOH + Cu2O

Mechanism

O O- O-
Cu2+ O
C R C 2+ C +
H -H 2O Cu C Cu
H H H
C C C C
- H H H H
.. R R H
:OH R
..

-
HO

-
O O -
- O
O +
C OH H C OH OH Cu
-Cu+ C
H C OH H
.C C
H C R Cu
+
Cu
2+
+ H
C H R
H R
H R

Principle of Benedict’s test

Benedict’s test is performed by heating the reducing sugar with Benedict‘s reagent. The presence
of the alkaline sodium carbonate converts the sugar into a strong reducing agent called
enediols. During the reduction reaction, the mixture will change its color from blue to brick-red
precipitate due to the formation of cuprous oxide (Cu2O). Copper in its cupric (Cu2+) or copper
(I) form is reduced to cuprous (Cu+) or copper (II). The red-colored cuprous oxide is insoluble in
water and hence, separated. If the concentration of the sugar is high, then the color becomes
more reddish, and the volume of the precipitate increases.

36 | P a g e
 Blue = No Aldehyde
Green/yellow = 0.5 - 1.0 % Aldehyde
Orange = 1.0-1.5 % Aldehyde
Red = 1.5 - 2.0 % Aldehyde
Brick red = Greater than 2.0 % Aldehyde

6- Haloform Reaction

Haloform reaction is given by those carbonyl compounds containing -CH3 group directly
attached with carbon atom of C=O.

O O

+ 3X2 + 4NaOH
R O
- + CHX 3 + 3NaX + 3H2 O
R CH3
O O

+ 3I2 + 4NaOH
R O
- + CHI 3 + 3NaI + 3H2 O
R CH3 Iodoform Yellow Solid

O O

+ 3Br2 + 4NaOH
R O
- + CHBr 3 + 3NaCl + 3H2 O
R CH3 Bromoform Pale Yellow Liq

37 | P a g e
Mechanism

O O + - O O
- Br Br
- -H 2O -H 2O
H3C
+ OH
H3C
..
CH 2 - H3C CHBr - H3C CHBr
CH2 -Br OH ..
-
H H

+ -
-Br- Br Br

O O O O
-Br- -H 2O
H3C CBr 2 - H3C
H3C CBr 3 + - H3C CBr 2 OH CHBr 2
..
- Br Br
H

-
OH

O- O O
-
+ :CBr 3
-
+ CHBr 3
H3C H3C OH H3C O
CBr 3
OH

38 | P a g e
7- Oxidation of Congugated Aldehyde With Nitrile or Cyanide/MnO2

This reaction is apecific for aldehydes.

- -
O O
-
+ CN -
H3C CH CH C H H3C CH CH C H
+
CN

+ H+

-
O O H
MnO2 
H3C CH CH C C N H3C CH CH C H
+ -2H
CN

+ H2O

- -
O O
H3C CH CH C C N + C2H 5OH
H3C CH CH C C N
+ - H2O
O
+
H O C2 H 5
H H

-
- CN

O + O
-H +
H3C CH CH C O C2 H 5 H3C CH CH C O C2 H 5
Ethyl but-2-enoate H
Conjugate Ester

39 | P a g e
8- Oxidative cleavage of Ketones with Alkaline KMnO4

Overall Reaction
O O O
-
R C CH2 R' KMnO 4/OH R C OH + R' C OH
[O]

Mechanism

OH HO
O
-
Tautomerism KMnO 4/OH
R C CH2 R' R C CH R' R C HC R'

HO OH

-H 2O

O O O O O

2OH [O]
R C OH + R' C OH R C C R'
-H 2O
R C CH R'

OH

40 | P a g e
9- Oxidation with SeO2

It is toxic, sublime solid.

It is used commonly to oxidize alkenes.

It can convert di-ketones into α,β-unsaturated di-ketones.

It can oxidize allylic group into allylic alcohol.

+IV +II 0
SeO2 SeO Se

White solid Red solid Black solid

O O
R2
R2 + SeO2
+ H2SeO

R1 R1 O

Mechanism

H Se O
O O O
+ H
R2 R2 -/+ H R2

R1 R1 R1
Se

O
OH - H 2O
Rearrangement

H
O O O O

R2 - H 2SeO R2 + H 2O R2

R1 O R1 R1
Se Se
O H
O

41 | P a g e
9- Oxidation of Aldehyde with Ag2O

When Ag2O is added to aldehydes, carboxylic acids are formed. This results in the
formation of silver metal layer (“Silver Mirror”), a reaction known as the Tollens test.
It is the reagent of choice for the oxidation of aldehyde into carboxylic acid and is used for the
selective oxidation of aldehyde, because it has no effect on the presence of other oxidizable
functional groups present in the aldehyde molecule.

O O

H Ag 2 O OH
NaOH

O O
H3C CH3 H3C CH3
H Ag 2 O OH
NaOH
CH3 CH3
O O

Keto-aldehyde Keto-acid

10- Oxidation of cyclic ketones

In this reaction cyclic ketones undergo ring expansion with per acid to yield cyclic ester.

(Oxidizing agent = mCPBA (meta-chloroperbenzoic acid), trifluoropercetic acid, etc)

H
O
O O
(3-chlorophenyl)(trioxidanyl)methanone

m-Chloroperbenzoic acid

Cl

42 | P a g e
 O
O
O CH2
H2C CH2 mCPBA
H2C CH2
H2C CH2 CH2 CH2
CH2
cyclohexanone oxepan-2-one

H3C H3C

H3C H3C

O O
mCPBA
O

Camphor α-Campholide

Oxidation of Carboxylic Acids

1- With Lead tetracaetate

First Method

It follows free radical mechanism.

Step 1 (Initiation Step)

O OAc O OAc
.. +IV +
Cu2 .. .. +IV

R OH + Pb OAc R O .. Pb OAc
.. -AcOH ..
OAc OAc
OAc

OAc
R
.
+ CO 2 + .
Pb OAc

OAc

43 | P a g e
Step 2 (Propagation Step)

There are two ways for further reaction of R’.

(i)

. O C CH3 OAc
. . . ..
R + Pb OAc R+ + CH 3COO
-
+ Pb

OAc OAc

(ii)

O
.
.O C .R OAc
. . .. .
Pb OAc Pb + CO 2 + R
OAc OAc

Step 3 (Termination Step)

(i)

. .
R + R R --- R

(ii)

+ -
R CH 3COO CH 3COOR

Second Method

44 | P a g e
 O OAc O OAc
.. +IV
..
R CH2 CH2 OH
.. + Pb OAc
-AcOH
R CH2 CH2 . . O Pb OAc

OAc Homolytic Cleavage OAc

OAc

O OAc
. . .
R HC CH 2 + CO 2 R CH2 CH2
..
O + Pb OAc
Heterolytic Cleavage :
OAc
H Homolytic Cleavage

2+
Cu

+
R CH CH 2 + H
+
+ Cu

Example: Oxidation of 1,2-dicarboxylic acid

R R AcO OAc O R R O OAc

HOOC C C COOH + Pb H
..
O C
..
C C
..
C O
..
Pb
. . OAc
-AcOH
R' R' AcO OAc R' OAc
R'

R R

: Pb (OAc) 2 + AcOH + 2CO2 + C C

R' R'

45 | P a g e
Example: Oxidation of α-hydroxy carboxylic acid

Oxidation of α-hydroxy carboxylic acid yields ketones.

R OAc OAc
O R O OAc
HO C C OH + Pb H
..
O C
..
C O
..
Pb
. . OAc
-AcOH
R' OAc OAc R' OAc

: Pb (OAc) 2 + AcOH + CO 2 + C O

R'

2- Oxidation of carboxylic acid with halogens

Hunsdiecker Reaction
The Hunsdiecker reaction (also called the Borodin reaction or the Hunsdiecker–Borodin
reaction) is a name reaction in organic chemistry whereby silver salts of carboxylic acids react
with a halogen to produce an organic halide. It is an example of both a decarboxylation and
a halogenation reaction as the product has one fewer carbon atoms than the starting material (lost
as carbon dioxide) and a halogen atom is introduced its place. The reaction was first
demonstrated by Alexander Borodin in his 1861 reports of the preparation of methyl
bromide (CH3Br) from silver acetate (CH3CO2Ag). Shortly after, the approach was applied to the
degradation of fatty acids in the laboratory of Adolf Lieben. However, it is named for Clare
Hunsdiecker and her husband Heinz Hunsdiecker, whose work in the 1930s developed it into a
general method. Several reviews have been published, and a catalytic approach has been
developed.
O
Br2
R -
O Ag + CCl 4
R Br + AgBr

46 | P a g e
Mechanism

The reaction mechanism of the Hunsdiecker reaction is believed to involve organic

radical intermediates. The silver salt of the carboxylic acid 1 will quickly react with bromine to
form acyl hypohalite intermediate 2. Formation of the di-radical pair 3 allows for
radical decarboxylation to form the dir-adical pair 4, which will quickly recombine to form the
desired organic halide 5. The trend in the yield of the resulting halide is
primary > secondary > tertiary.
O O O
Br2 . . .
. . Br . . .. . Br R Br
- + CCl 4 R O R O - CO 2
R O Ag
4
1 2 3

R-Br
5

Oxidation of Amines

1- Oxidation of Primary Amines with H2O2

Mechanism

HO
-
.. O .. H + .. +OH ..
H3C CH2 NH2 + H O
-OH
- H3C CH2 N H
-H 2O
H3C CH2 N OH
H H
Heterolytic cleavage Heterolytic cleavage
.. -
HO O H -OH

OH HO
-
+OH +
H3C CH N OH H3C CH N: H3C CH2 N OH
-H 2O -H 2O :
Oxime
H OH
H
Dehydration Heterolytic cleavage

47 | P a g e
2- Oxidation of Amines with Peracids

(i) Primary amines

-
O
Step-wise reaction + 
H3C CH2 NH2 + 3CH3COOOH
- 3CH3COOH
H3C CH2 N OH
HO

-
O

+
H2O + H3C CH2 N

(ii) Tertiary amines

H3C H3C
.. + -
H3C N + ArCOOOH H3C N O + ArCOOH

H3C H3C

3 mine oxide

R' R' R'

+ - + -
R N: + HO-OH / CH 3COOOH R N OH + OH R N O + H2O

R'' R'' R''


3 mine oxide

48 | P a g e
3- Oxidation of Amines with HNO2 (Nitrous Acid)

HCl + NaNO 2 NaCl + HNO 2

HNO 2 = HONO

+
H
 .. ..
HNO 2 0  C + - -H2O ..
R NH2 R N N O OH R N N O
+
N=O
H H

+ -H2O +
R N N + H
R N N O H R N N OH
H

-N 2

+ H2O
R R-OH

4- Oxidation with KMnO4

-
O O H
KMnO 4 + IOI
H3C NH2 H3C N H H3C N H H3C N O
- H 2O
H

IOI

H3C NO 2

Alkaline
2 NH2 N N
KMnO 4

49 | P a g e
5- Oxidation with MnO2/H2SO4
O
NH2

+ 2MnO 2 + 3H2SO4 + 2MnSO4 + 2H2O + NH 4HSO4

Oxidation of Hydrazines

Hydrazine is readily oxidized to nitrogen in the presence of one electron oxidants like Cu2+.
Mono-substituted hydrazines react with one electron oxidants like Cu(II) or Fe(III) to give
unstable azo compound which decompose with the loss of nitrogen to hydrocarbon.

Mechanism

.. ..
2+
NH NH2 Cu N N H 
-H2
+ N2

Intermediate

Acyl hydrazines are decomposed by the two electron oxidants like Cl 2 and Br2 giving diazonium
salts like;

+
NH NH2 N N -
+ 2Cl2 Cl + 3HCl

Diazonium salt

50 | P a g e
Oxidation of Hydrazones

Hydrazones are oxidized to diazo alkanes mercury (II) oxide. Those containing aryl substituents
give moderately stable products (due to conjugation) which can be separated/isolated e.g.
benzopenone hydrazone gives stable diazomethane in nearly quantitative yields (100%).

Mechanism
.. .. .. ..
C N NH2 HgO C N NH Hg OH

C6H5 C6H5

+ - +
C N N C N N H 0 -
-H 2O + Hg + OH
C6H5 H5 C6
 h
-N 2

..
C
Diphenyl carbene

Oxidation of Aromatic Systems

Oxidation of Alkyl side chain of Aromtic compounds

51 | P a g e
1- With Chromyl Chloride / Etard Reaction
Mechanism
.. .
CH2 H O .. Cl CH2 HO Cl

+ Cr + Cr
O Cl O Cl
CH3 CH3

.
CH O Cl CH2 HO Cl
.
. Cr + .
. Cr
H
HO Cl O Cl

CH3 CH3
O Cl
Cr
O Cl Cl

O Cr. Cl
..
. OH
CH O Cl HO Cl HC
OH
Cr + Cr

HO Cl O Cl O Cr Cl

CH3
Cl
CH3

..
H2O

O H +
O H

OH HC OH
CH
Cl Cl
O Cr O Cr Cl
- Cl -
O Cr. Cl + + O Cr. Cl
H Cl Cl
OH OH
CH3 CH3

C H OH

+ HO Cr Cl

Cl
CH3

52 | P a g e
2- With p-Nitrosodimethyl aniline
CH3 N O CHO NH2
NO 2 NO 2
H2O
+ +

NO 2 NMe 2 O 2N NMe 2

Mechanism
H H
H +
-
N O H2C O N O H CH2 O O N CH
+ +
N N - NO 2
- O
O .
+ +
NMe 2 NMe 2 NO 2 NMe 2
NO 2 NO 2

- H 2O

H H O
H H O
N CH
N H C N CH
NO 2
NO 2 NO 2
+H-OH
+
NMe 2 NO 2
NMe 2 NMe 2 NO 2
NO 2

Oxidation of Aromatic Rings

53 | P a g e
 O

V 2O 5
2 + 9O2
o
2 O + 6H2O + 6CO2
300 C

O O

HC C OH
O + H2O
HC C OH
O
O

Maleic Acid

COOH
KMnO4
H+
COOH

Phthalic acid

O 3 + V 2O 5
O


O
Phthalic anhydride

COOH
O3 + 
Zn / H 2O2
COOH
Phthalic acid

O3 COOH
COOH

Diphenic Acid

54 | P a g e
 O

CrO3 / H 2O

O Naphthoquinone

COOH COOH
CaO / 
CrO3 / H 2O
or KMnO 4 / H
+
Decarboxylation + CaCO3
N N COOH N

Oxidation of Benzylic System

CH3 CH3 COOH

K2Cr2O7 / H 2SO4
+ H2 O

CH2 CH3 COOH

K2Cr2O7 / H 2SO4
+ CO2 + 2H2O

CH3 COOH

K2Cr2O7 / H 2SO4

CH3 COOH Terephthalic acid

55 | P a g e
Chapter 2: Reduction
Reduction of Alkynes

1- Birch Reduction

It is used for partial hydrogenation of alkynes.

It follows free radical mechanism. (Homolytic cleavage)

It gives trans-alkenes.

+e
. . Na / Liq NH 3 . -
R C C R' -33 C R C C R' R C C R'

-33 C

+[H]

R H H H
+[H] - +e .
C C R C C R C C
H R' R' R'

Trans-Alkene

2- Hydrgenation of Alkynes using Lindlar Catalyst

It performs partial hydrogenation of alkynes.

It gives cis-alkenes.

Lindlar Catalyst: Lindlar catalyst is a heterogeneous catalyst that consists of palladium deposited
on calcium carbonate which is then poisoned with various forms of lead or sulphur. It is used for
the hydrogenation of alkynes to alkenes (i.e. without further reduction into alkanes) and is named
after its inventor Herbert Lindlar.

5% Pd - CaCO 3 Pb(OCOCH 3)2

N
Lead acetate Quinoline

The catalyst is used for the hydrogenation of alkynes to alkenes (i.e. without further reduction
into alkanes). The lead serves to deactivate the palladium sites, further deactivation of the

56 | P a g e
catalyst with quinoline or 3,6-dithia-1,8-octanediol enhances its selectivity, preventing formation
of alkanes. Thus if a compound contains a double bond as well as a triple bond, only the triple
bond is reduced.
Alkyne hydrogenation is always stereoselective, occurring via syn addition to give the cis-
alkene. For example the hydrogenation of acetylene-dicarboxylic acid using Lindlar catalyst
gives maleic acid rather than fumaric acid.

R R'

Quinoline
R C C R' + H2
BaSO4
C C

H H
Cis - Alkene

Mechanism

3- Hydrogenation of Alkynes with Adkins Catalyst

Copper chromite is an inorganic compound with the formula Cu2Cr2O5. It is a black solid that is
used to catalyze reactions in organic synthesis. The material was first described in 1908. The
catalyst was developed in North America by Homer Burton Adkins and Wilbur Arthur Lazier,
partly based on interrogation of German chemists after World War II in relation to the Fischer-
Tropsch process. For this reason it is sometimes referred to as the Adkins catalyst or the Lazier
catalyst.

57 | P a g e
The compound adopts a spinel structure. The oxidation states for the constituent metals are
Cu(II) and Cr(III). A variety of compositions are recognized for the substance, including
Cr2CuO4.CuO.BaCrO4 and Cr2Cu2O5. Commercial samples often contain barium oxide and other
components.

Copper chromite is produced by thermal decomposition of one of three substances. The

traditional method is by the ignition of copper chromate.

2CuCrO4 → 2CuCrO3 + O2
Copper barium ammonium chromate is the most commonly used substance for production of
copper chromite. The resulting copper chromite mixture produced by this method can only be
used in procedures that contain materials inert to barium, as barium is a product of the
decomposition of copper barium ammonium chromate, and is thus present in the resulting
mixture. The by-product copper oxide is removed using an acetic acid extraction, consisting of
washing with the acid, decantation and then heat drying of the remaining solid to yield isolated
copper chromite. Copper chromite is produced by the exposure of copper barium ammonium
chromate to temperatures of 350-450 °C, generally by a muffle furnace.

Ba2Cu2(NH4)2(CrO4)5 → CrCuO3 + CuO + 2Ba + 4H2O + 4Cr + N2 + 6O2

Copper ammonium chromate is also used for production of copper chromite. It is generally
utilized as an alternative to the route of barium ammonium chromate for usage in chemicals
reactive with barium. This can also be washed with acetic acid and dried to remove impurities.
Copper chromite is produced through the exposure of copper ammonium chromate to
temperatures of 350-450 °C:
Cu(NH4)2(CrO4)2 → CrCuO3 + CrO + 4H2O + N2
An active copper chromite catalyst which includes barium in its structure can be prepared from a
solution containing barium nitrate, copper(II) nitrate, and ammonium chromate. When these
compounds are mixed a resulting precipitate is formed. This solid product is then calcined at
350–400 °C to yield the catalyst:
Cu(NO3)2 + Ba(NO3)2 + (NH4)2CrO4 → CuCr2O4·BaCr2O4

4- Hydrogenation with Raney Nickel

58 | P a g e
Raney nickel also called spongy nickel is a fine-grained solid composed mostly of nickel derived
from a nickel–aluminium alloy. Several grades are known, of which most are gray solids. Some
are pyrophoric, most are used as air-stable slurries. Raney nickel is used as a reagent and as a
catalyst in organic chemistry. It was developed in 1926 by American engineer Murray Raney for
the hydrogenation of vegetable oils.

Alloy preparation
.The Ni–Al alloy is prepared by dissolving nickel in molten aluminium followed by cooling
(quenching). Depending on the Ni-Al ratio, quenching produces a number of different phases.
During the quenching procedure, small amounts of a third metal, such as zinc or chromium, are
added to enhance the activity of the resulting catalyst. This third metal is called a
"promoter". The promoter changes the mixture from a binary alloy to a ternary alloy, which
can lead to different quenching and leaching properties during activation.

Activation

In the activation process, the alloy, usually as a fine powder, is treated with a concentrated
solution of sodium hydroxide. The simplified leaching reaction is given by the
following chemical equation:

2 Al + 2 NaOH + 6 H2O → 2 Na[Al(OH)4] + 3 H2

Ni-Al + NaOH + H2O -------- Ni + NaAlO2 + 3/2H2

The formation of sodium aluminate (Na[Al(OH)4]) requires that solutions of high concentration
of sodium hydroxide be used to avoid the formation of aluminium hydroxide, which otherwise
would precipitate as bayerite.

Raney Nickel
H2C CH2 + H2
150 oC
H3C CH3

H2C CH2
Raney Nickel
+ H2
150 oC
H3C CH2 CH2 CH3
H2C CH2

59 | P a g e
5- Wilkinson’s Catalyst
Wilkinson’s Catalyst [IUPAC Name: Chlorotris(triphenylphosphine)rhodium(I)] is a
coordination compound whose coordination centre is rhodium. It is extensively used as a catalyst
in the hydrogenation of alkenes. The chemical formula of Wilkinson’s catalyst can be written as
[RhCl(PPh3)3] where ‘Ph’ denotes a phenyl group. At ambient temperatures, this coordination
complex exists as a reddish-brown solid.
Wilkinson’s catalyst is named after the English chemist Sir Geoffrey Wilkinson. It has square
Lewic Acid= electron pair acceptor (Rh); Lewis Base = Electron pair donor (Cl-, PPh3)

During the synthesis of Wilkinson’s catalyst, one equivalent of triphenylphosphine reduces

rhodium(III) to rhodium(I) while three other equivalents bind themselves to the metal as ligands
in the final product.
4P(C6H5)3 + RhCl3(H2O)3 → RhCl(P(C6H5)3)3 + OP(C6H5)3 + 2HCl + 2H2O

Mechanism of Catalysis for the Hydrogenation of Alkenes

i. Initially, a 14-electron or 12-electron complex is formed from the dissociation of 1 or 2
triphenylphosphine ligands.
ii. Now, the oxidative addition of molecular hydrogen (H2) to the metal core of Wilkinson’s
catalyst (rhodium) occurs.
iii. The third step of the mechanism involves the formation of a pi complex with the alkene.
iv. The hydrogen is inserted into the complex via migratory insertion which could proceed
through intramolecular hydride transfer or through olefin insertion.
v. Finally, reductive elimination occurs at the pi complex to regenerate the catalyst and
afford the required alkene product.

60 | P a g e
 PPh 3
Ph 3P
Rh
Cl
Ph 3P

-PPh 3 +PPh 3

PPh 3

Cl Rh
CH3 H2

PPh 3
CH2
R

Cl
Cl
PPh 3
PPh 3
Ph 3P Rh
CH2 Rh

PPh 3 H
CH2 H
H
R

Cl

Ph 3P PPh 3

Rh
H2C
. H
CH
H H2C CH
R
R

Ethene cannot be reduced by this method because ethene forms complex with Rhodium. Only
alkenes and alkynes are reduced and other common functional groups are not reduced (like C=O,
Nitrile, NO2, etc)
Hydrogenolysis does not occur.
Due strong affinity with CO aldehydes are degraded, e.g.

61 | P a g e
 O
O
CH2

H + H2 + Rh(PPh 3)Cl + H
C
H

6- Clemmensen reduction

Clemmensen reduction is a chemical reaction described as

a reduction of ketones (or aldehydes) to alkanes using zinc amalgam and
concentrated hydrochloric acid. This reaction is named after Erik Christian Clemmensen, a
Danish chemist. The original Clemmensen reduction conditions are particularly effective at
reducing aryl-alkyl ketones, such as those formed in a Friedel-Crafts acylation. The two-step
sequence of Friedel-Crafts acylation followed by Clemmensen reduction constitutes a classical
strategy for the primary alkylation of arenes. With aliphatic or cyclic ketones, modified
Clemmensen conditions using activated zinc dust in an anhydrous solution of hydrogen chloride
in diethyl ether or acetic anhydride is much more effective.

The substrate must be tolerant of the strongly acidic conditions of the Clemmensen reduction
(37% HCl). Several alternatives are available. Acid-sensitive substrates that are stable to strong
base can be reduced using the Wolff-Kishner reduction; a further, milder method for substrates
stable to Hydrogenolysis in the presence of Raney nickel is the two-step Mozingo reduction.

O
H H
Zn(Hg)
C C
HCl R R
R R

62 | P a g e
Mechanism
.. o +
O + Zn Zn
O H
OH

C + +
H C
C
.
R R 1e Transfer from Zn
R R
R R
Oxonium ion

..
Zn

+ o
Zn Zn OH
R R R R
- + + .
C C +H .
R C Zn
1e Transfer from Zn -H 2O
+ ..
Zn Zn R
1e Transfer from Zn to C takes place

+
+H

H H

+
+H 2+
R C R
R C R + Zn

+ H
Zn
1e Transfer from Zn to C takes place

63 | P a g e
Mechanism
.. o +
O + Zn Zn
O H
OH

C + H
+
C
C
.
Ph Ph 1e Transfer from Zn
Ph Ph
Ph Ph
Oxonium ion

..
Zn

+ o
Zn Zn OH
Ph Ph Ph Ph
- + + ..
C C +H Ph C Zn
1e Transfer from Zn -H 2O
+
..
Zn Zn Ph
1e Transfer from Zn takes place

+
+H

H H

+
+H 2+
Ph C Ph
Ph C Ph + Zn

+ H
Zn
1e Transfer from Zn to C takes place

Strongly hindered ketones give poor yields.

64 | P a g e
7- Wolff-Kishner Reduction
It is the reduction of aldehydes and ketones to alkanes. Condensation of the carbonyl compound
with hydrazine forms the hydrazone, and treatment with base induces the reduction of the carbon
coupled with oxidation of the hydrazine to gaseous nitrogen, to yield the corresponding alkane.
The Clemmensen Reduction can effect a similar conversion under strongly acidic conditions, and
is useful if the starting material is base-labile.

NH2
O N

CH3 H2NNH2 CH3 CH3

KOH
-H2O -N2

65 | P a g e
Mechanism of the Wolff-Kishner Reduction
..
NH2 ..
H NH2
+ ..
O - N H N
H
+ .. ..
CH3 H2NNH 2 CH3 CH3
-
O OH

-H 2O

H H
H -
:N : :N
.. N : :N :N H
N
-
C- CH3 OH CH3
.. CH
3 -H 2O

- OH H - OH

.. .. -
N H N:
:N :N
H H H ..-
C C C
CH3 - CH3
+ OH -N 2 CH3
- H 2O

+ H-OH
- OH

H H
C
CH3

66 | P a g e
8- Mozingo Reduction

The carbonyl compounds aldehydes and ketones are converted with ethane-1,2-dithiol in the
presence of Lewis Acid into its dithio-acetal or ketal which is then hydrogenolyzed over Raney
Nickel at high temperature.

Mechanism
H
R R +
HS CH2 S CH2
+ - - +
(Et2O . BF3)
O +
HS CH2 HS CH2
R R -
O
Ethane-1,2-dithiol

R R R
HS CH2 S CH2 S CH2
H
H2 / Ni -H 2O
+ 200 C
o
H
HS CH2 S CH2 S CH2
R R R H
O H

Mozingo reaction is useful for reducing carbonyl compounds which are sensitive to mineral acid
and bases.
Reduction of Carboxylic acid with borane

Reduction of carboxylic acid with di-borane produces alcohol.

Mechanism

67 | P a g e
 H
H -
- B H
B H
H H
.. H +
O
+
B H O
H O H
H
R C OH + B H R C OH
-H 2
R C O B
H
H

B
O H
H H H H
H OH H OH R C O B
R C O H R C O B
- BH(OH) 2
H H
H H H

+
OH

B
H H

Rosenmund’s Reaction

It consists of acid halides with H2 on palladium catalyst supported on

BaSO4 in refluxing (boiling) xylene or toluene. Poisoning of catalyst is helpful in this reaction.

O O

Cl H
H2 / Pd
BaSO4 (Poisoned)
Xylene

Naphthyl chloride Naphthaldehyde

Wallarch Reaction

68 | P a g e
 It is used to prepare mixed amines. In this method on aldehyde is reacted
in the presence of formic acid with primary or secondary amine secondary or tertiary amine. This
reaction is carried out at elevated temperature.

R C H + HCOOH + R' - NH 2 R CH2 NH R'

Emde Reduction

It is a reduction of amine group (-NH2) with the cleavage of C-N bond. An

alternative method of this reduction is Hoffmann degradation reaction. In this method
heterocyclic ring is first methylated and then treated with hydroxide (AgOH). The hydroxide
removes hydrogen as water and ring is cleaved.

Example I
H H H
H H H H
CH3 - I -
AgOH HO
+ - AgI - H 2O CH2
N +
N N N
-
H I H CH3 H CH3 H CH3

Example II
H H H
H H H H
CH3 - I -
AgOH HO
+ - AgI - H 2O CH2
N N +
-
N N
H I H CH3 H CH3 H CH3

Leukart Reaction

The Leuckart reaction is the chemical reaction that converts aldehydes or

ketones to amines by reductive amination in the presence of heat. The reaction, named
after Rudolf Leuckart, uses either ammonium formate or formamide as the nitrogen donor
and reducing agent. It requires high temperatures, usually between 120 to 130 °C; for the
formamide variant, the temperature can be greater than 165 °C.

Mechanism

69 | P a g e
 O H O
+
H C
-
H N H H C + NH3
O H OH

- H
O H O O
C + :N H
R1
C
R2
C
R1 R2 R1 R2
H
+
H N H N
H H
H

O O
- H C H C
-
O OH

H O
H + H
H C O
R1 C R2 +
O- R1 C R2 C
CO2 + H2O + N - H 2O R1 R2
H H N
H H N
H H

Reduction of nitriles
Mechanism

70 | P a g e
 H
- H
H Al H
.. + + C Li
R C N + Li R C N Li H
R N
-AlH 3
Hydride Addition Imine

AlH 2 - H

H H H
C H C H C Li
H - OH H - OH
R N R N R N
H -AlH 2(OH) H - LiOH H
H AlH 2 AlH 2
Pri - Amine

Reduction of N-Nitroso Compounds

These compounds are reduced by mild electron transfer reagent to substituted hydrazine e.g. N-
Nitroso-N-phenylhydrazine with zinc in acetic acid gives 5% of N-methyl-N-phenylhydrazine.

CH3 CH3
N N
NO NH2
Zn / CH 3COOH
Mild

CH3 CH3
N N
NO H
Zn / CH 3COOH
Strong + NH3 + H2O

Reduction of Azo Compounds

Azo compounds can be reduced by using two different methods:

(i) LiAlH4

(ii) Na2S2O4 / CH3COOH

71 | P a g e
(i)
N N NH NH
LiAlH4
AlCl3

(ii) Na2S2O4 in CH3COOH can reduce the azo compound into amines, but with cleavage of N
double bond N (N=N).

N N NH2 H2N
Na 2S2O4
CH3COOH
+

N N NH2 H2N
Na 2S2O4
CH3COOH
+
O 2N O 2N

Stephen Reduction
The nitriles can be reduced to aldehydes by different methods. In this
method nitriles, and then treated with Sn + HCl in anhydrous ether, followed by hydrolysis.

Mechanism

72 | P a g e
  
..   + -
H5C2 C N + H Cl H5C2 C N H + Cl

Sn + HCl
H5C2 C N H o H5C2 C N H
20 C / Ether
-HCl
H Cl
 
 
H - OH


OH H OH H

+ H-Cl + -
H5C2 C N H5C2 C N H + Cl

H H H
H

C
+ NH 4Cl
H5 C2 H

Q: (Exercise) Write mechanism of Stephen reduction for the following compounds?

C N C N

and

Sonn-Muller Reaction

73 | P a g e
 The Sonn-Muller Reaction involves conversion of anilide or toluidide into
imine chloride which is reduced to imine with tin chloride which is then hydrolyzed to obtain
aldehyde.

Mechanism

.. O
O
NH2

C + -HCl C
H3C NH
R Cl

Cl OH

C C
PCl3
H3C N H3C N

HCl SnCl2

H
O
NH2
C +
H / HOH
H3C N C +
R H

Eschweiler Clarke Reaction

In this method a tertiary amine is prepared from a primary amine

or ammonia. In this method an amine is heated with formaldehyde and formic acid under reflux
(100 ºC).

Mechanism

74 | P a g e
 -
O H O
+
H3C CH2 NH2 + H
C
H
H3C CH2 N C H

H H

Proton Shifting

O O H
O
- + H C O H H C
H C O + H3C CH2 N C H
-H 2O
3 CH2 NH C H

H H H

O H
-
O
H C H +
CO2 + H3C CH2 N CH3 H3C CH2 N C H

H CH3 H
Sec - amine

Proton Shifting

O O OH
- + H C O H
H C O + H3C CH2 N C H
-H 2O
H3C CH2 N C H

CH3 H CH3 H

CH3
CO2 + H3C CH2 N

CH3
tert - amine

75 | P a g e
76 | P a g e
77 | P a g e
78 | P a g e
79 | P a g e
80 | P a g e
20,27,34,37

81 | P a g e