Oxidizing Agents

There are many available oxidizing agents for the oxidation of the organic
compounds. But the main focus of this chapter is the oxidation reaction using-

 Chromium(Cr) and Manganese(Mn) compounds

 Seleniuom dioxide(SeO2)
 Lead tetra acetate(Pb(OAc)4)
 Peracids (RCOOOH)
 Periodate
Oxidation with Chromium and Manganese compound

Among the variety of agents available for the oxidation of organic compounds,
the most commonly used are the derivatives of hexavalent chromium (CrVI) and
heptavalent manganese (MnVII).
CrO3 and Na2Cr2O7/ K2Cr2O7 are converted to Cr3+ by the net transfer of three
electrons to each chromium atom. The oxidation with KMnO4 in acetic media
produce Mn2+ by a net transfer of five electros to each manganese atom. In
basic or neutral media, MnO2 is formed.

2CrO3 + 3R2CHOH + 6H+ 3R2C=O + 2Cr3+ + 6H2O

2MnO4- + 5R2CHOH + 6H+ 5R2C=O + Mn2+ + 8H2O

2MnO4- + 3R2CHOH 5R2C=O + MnO2 + 2H2O + OH-

These oxidizing agents are used as aqueous solution. But the organic
compounds to be oxidized is not soluble in water, some co-solvent such as
t-butylalcohol, acetic acid, acetic anhydride, pyridine are used. But ethanol or
acetone are not used since they are easily attacked by KMnO4.
Oxidation with Chromium and Manganese compound

Alternatively, the anhydrous chromium-trioxide-pyridine complex is particularly

useful. The complex is soluble in both pyridine and various chlorinated solvent
such as CH2Cl2.
O

CrO3 + -18 to -15 oC

N Cr O
N 2
O

80% precipitated
Red Crystal

Upon exposure to water, this anhydrous complex rapidly turns into yellow
crystalline solid hydride (C19H12Cr2N2O7) which is no longer soluble in
chlorinated solvent.
Solution of hexavelent chromium compounds in aqueous mineral acids or
mixture of acetic acid and mineral acids contain an equilibrium mixture of the
acid chromate and dichromate ion.

2 HCrO4- H2O + Cr2O72-

Oxidation with Chromium and Manganese compound

Studies of the mechanism of Cr and Mn compounds is complicated by the fact

that the oxidation of most organic compounds is accompanied by the net
transfer of two electros although the oxidizing agent can accept a total of three
or five electron.

It therefore, evident the intermediate valance state of chromium and

Manganese are in the overall process.

CrVI + R2CHOH R2C=O + 2H+ + CrIV

CrIV + CrVI CrV

CrV + R2CHOH R2C=O + 2H+ + CrIII

Oxidation of Alcohol with Cr and Mn compounds

The probable mechanism of oxidation of alcohol by CrVI is outlined as follow.

O
H+
(CH 3 ) 2 CHOH + HCrO 4 - (CH 3 ) 2 CH-O Cr OH + H 2O
fast
O

O
slow
(CH 3 ) 2 -C-O Cr OH (CH 3 ) 2 C=O + H 3O + + HCrO 3 -
Rate limiting
H O
H 2O

With unhindered alcohol, the initial equilibrium to form the chromate ester fast
and the subsequent decomposition of chromate ester form the product which is
rate limiting.
Oxidation of Alcohol with Cr and Mn compounds

Tertiary alcohol are usually relatively inert to the oxidation by chromic acid.
Failure of an alcohol to be oxidized by chromic acid is often cited as evidence
that it is tertiary alcohol.
However, tertiary 1,2 diols are very rapidly cleaved by chromic acid if they are
sterically capable of forming cyclic chromate ester.

CH3 CH3 O CH3

OH N a 2 C r2 O O Cr OH O O
7
H C lO 4
Cr
OH OH O
O O
CH3 CH3 CH3

CH3

O
85%
O

CH3
Oxidation at Allylic Carbon

In olefins oxidation, allylic oxidation become favorable, if chromium trioxide

dipyridine complex is used.

The reaction is believed to proceed by the formation of allylic radical

intermediate and the major product is formed by the removal of tertiary allylic
hydrogen.
Oxidation with Selenium Dioxide (SeO2)

SeO2 is a poisonous white crystalline solid. In aqueous media, it is

converted to selenious acid, (OH)2SeO. During oxidation Se(IV) ion
converted to metallic selenium, a red-black solid.

The common uses of SeO2 are;

 The conversion of Aldehyde and ketone to 1,2-dicarbonyl

 The conversion of 1,4-dicarbonyl to 2,3-unsaturated -1,4-dicarbonyl
 The conversion of olefin to allylic alcohol derivative

 Conversion of aldehyde and ketone to 1,2-dicarbonyl compounds

O O O
H2 SeO2
C6H5 C C C6H5 C6H5 C C C6H5
H2O, dioxane
reflux
Mechanism for the oxidation of monocarbnyl by SeO2

OH
Step-1: SeO2 + H2O H2SeO3 or Se O
OH
OH
Se O HO
OH Se O
Step-2:
O O H
H -H2O
C6H5 C C C6H5 C6H5 C C C6H5

H
HO

Step-3: Se O O
O -H2O
O C6H5 C C C6H5 + Se
C6H5 C C C6H5

H
Oxidation with Selenium Dioxide (SeO2)

Examples: O O O
SeO2
C6H5 C CH3 C6H5 C CH
H2O, dioxane
reflux

O O O
O OH
H2SeO3
H2O, dioxane
reflux
25-30oC

 Conversion1,4-dicarbonyl to 2,3-unsaturated -1,4-dicarbonyl

O O O O
H2 H2 SeO2
C6H5 C C C C CH3 C6H5 C C C C CH3
H2O, CH3COOH H H
90oC
Conversion of 1,4-dicarbonyl to 2,3-unsaturated -1,4-dicarbonyl
OH
Se O HO
Se O
OH
O O O O
H H -H 2 O H
C 6H 5 C C C C CH3 C 6H 5 C C C C CH3
H
H H H
-H 2 O
O O
Examples: Se8 + C 6H 5 C C C C CH3
CH3
H H
CH3 CH3
CH3
CH CH3
CH
H CH3
O O O
H H CH3
O
H3C H

The dehydrogenation process in more rapid when the two hydrogen being
removed bear the cis-relationship than trans.
This observation was initially regarded as evidence for the mechanism in which
two hydrogens are removed simultaneously be SeO2.
Oxidation of Olefin by SeO2

Oxidation of olefin with SeO2 at allylic position

O H
H 2 SeO 2
C 6H 5 C C C C 6H 5 C 6H 5 C C C C 6H 5
H 2O , A cO H H H
H H 1 1 5 oC H

H+
Mechanism: OH

HO Se O O Se OH
H2 S eO 2 H
C 6H 5 C C C C 6H 5 C 6H 5 C C C C 6H 5 C 6H 5 C C C C 6H 5
H 2 O , A cO H H H H
H H 115 o C H H H

OH
H 2O
C 6H 5 C C C C 6H 5 C 6H 5 C C C C 6H 5
H H H H
H H

C 6H 5 C C C C 6H 5
H
H H
Oxidation of Olefins by SeO2

Some more Examples:

OH O
CH3 CH3 CH3
SeO2
C2H5OH

35% 27%

CH3 CH3
CH3 CH2OH
H H
SeO2, H2O OH
OH
H
dioxane, reflux + +

H CH(CH3)2 H CH(CH3)2
H CH(CH3)2 H CH(CH3)2
48% 20% 23%
Oxidation with Lead tetra acetate; Pb(OCOCH3)4
Lead tetra acetate Pb(OCOCH3)4 is commercially available crystalline
solid. Infra-red spectra suggest that both oxygen atom of each acyloxy
group are coordinated with the lead atom. The crystalline complex
formed when the tetra acetate is treated with good donor such as
pyridine.

O
C6H6 O OCOCH3
H3C C Pb
+ H3C C Pb
O 4
N O N
3

40-60%

Although Pb(OCOCH3)3 may be employed for the oxidation of wide variety of

organic compounds, the primary uses of Pb(OCOCH3)4 has been for;
 The oxidative cleavage of 1,2-diols
 The oxidative cleavage of α-hydoxyketone
 The oxidative cleavage of 1,2-diketone
 The oxidative cleavage of α-hydoxyacid
Oxidation with Lead tetra acetate; Pb(OCOCH3)4

Pb(OCOCH3)4 serves as reagent used in non-aqueous media to accomplish the

same type of oxidation effected by periodate with water soluble compounds.
Being a more strong oxidizing agents, Pb(OCOCH3)4 will cleave certain classes
of compounds which are oxidize very slowly with periodates.
The rapid reaction of this reagents with molecule having hydroxyl group prevent
the uses of water and alcohol as solvent. The acetoxy residue of lead
teraacetate also equilibrate rapidly with acyloxy group of other carboxylic acids
The cleavage of 1,2-diols by Pb(OCOCH3)4

The preferred pathway for cleavage of 1,2-diols involves the formation of cyclic
intermediate which decomposes to the carbonyl compounds as follow

H2 H2
H C 6H 5 O C CHO
P b(O C O C H 3 ) 4 C 6H 5 O C C CH2
H2 A dded slow ly +
H
C 6H 5 O C C CH2 O O C H 2O
C 6H 6, 25 o C
OH OH Pb +
H 3C O C O OCOCH3
P b(O C O C H 3 ) 2

C yclic interm ediate

Since Pb(OCOCH3)4 may react further with the initial cleavage product, it is
normally best to ad oxidant slowly so that product are not contact with excess of
Pb(OCOCH3)4 during the course of reaction.

H
Pb(OCOCH3)4
H2C C (CH2)8 C CH2 H2C C (CH2)8 CHO + CH2O
H H
CH3COOH, 50oC
OH OH
The cleavage of 1,2-diols by Pb(OCOCH3)4

C O 2C 4H 9-n
P b (O C O C H 3)4
HC OH A d d e d s lo w ly
2 n -C 4H 9C O 2-C H O
o
C 6H 6, 2 5 -3 0 C
CH OH

C O 2 C 4H 9-n

The preference for the formation of cyclic intermediate can give significant
difference in rate of oxidation of diastereomeric 1,2-diols

Why cis-1,2-cyclopentadiol oxidize 3000 time faster than tans-1,2- cyclopentadiol

by lead tetra acetate? Explain.
The cleavage of 1,2-diols by Pb(OCOCH3)4

H H
Pb(OCOCH 3)4
H H
CH3COOH, 25oC
OH Rel. rate>3000 O
OH O OHC-(CH 2)3-CHO
Pb +
OCOCH 3
cis-1,2-cyclopentadiol Pb(OCOCH 3)2
H 3COCO
+
H2O
OH O Pb(OCOCH 3)2
Pb(OCOCH 3)4
H H OCOCH 3
CH3COOH, 25oC
H Rel. rate=1 H

OH O H

trans-1,2-cyclopentadiol -
OCOCH 3( or pyridine)

The cis-isomer could be incorporate into five membered ring intermediate and the
oxidation proceed smoothly.
On the other hand, the trans-isomer could not be incorporated into a five
membered ring without the introduction of substantial strain. Therefore, the
reaction proceed in other mechanism.
The cleavage of 1,2-diols by Pb(OCOCH3)4

In some cases, the cleavage of trans 1,2-diols formation of cyclic intermediate

seems mostly unlikely. Although such trans diols react more slowly than the
corresponding cis-diols, it is of the interest that are cleaved at all.

Further more, it is noted that trans-1,2-

diols which are cleaved only very slowly
with lead tetraacetate in acetic acid, are
more readily cleaved if pyridine is used
as solvent. These observation suggest
that the second mechanism for glycol
cleavage is possible which does not
require a cyclic intermediate.

An interesting application of this type of cleavage to the preparation 10

membered ring lactone. CO3H
OH O
COOH
Pb(OCOCH3)4
(C2H5)2O, H2O Benzene, 25oC
O O O
0-25oC
OH O
The cleavage of 1,2-diols by Pb(OCOCH3)4

OH OH O
Pb(OCOCH 3 ) 4
CH 3 COOH, 20oC
OH
Relative rate= 100

OH O

OH O
OH
Pb(OCOCH 3 ) 4
CH 3 COOH, 20 o C
Relative rate= 1
OH O
OH
Oxidation with Peracid (RCOOOH)
Oxidation with peracids have been used most extensively for the selective
oxidation of cabon-cabon double bond. They also slowly convert ketone to
ester. Other oxidations includes the oxidation of allylic or other activated C-H
bonds
In general, peroxidies reagents accomplish the oxidation of functional groups
that are frequently difficult to oxidize using Cr and Mn compounds
The most useful reagents are peracetic acid, peroxytrifluoroacetic acid and
perbenzoic acid.
O O O

H C O OH H3C C O OH F3C C O OH

Performic acid Peracetic acid

Peroxytrifluoroacetic acid

O O

C O OH C O OH

Perbenzoic acid
X COOH
X= H, Cl Perphthalic acid or
2-Carboxyperbenzoic acid
Oxidation of C=C bond with peracids
The reaction of olefins with per acids to form epoxides provides a convenient
and selective method for the oxidation of carbon-carbon double bond in the
presence of hydroxyl and carbonyl functional group.

H C 6H 5-C O 3H H
C 6H 5 C CH 2 C 6H 5 C CH 2
C H C l3
0 oC
O
6 9 -7 5 %

Although amines are readily attacked by peracids, unsaturated amides may be

oxidized without difficulty. Acid sensitive oxaziranes may be obtained by the
reaction of iminies under careful controlled condition.
Oxidation with Peracid (RCOOOH)
If only carboxylic acid used, the formation of ester depends on the strength of
acid to protonate the epoxide. For example, formaic acid and trifluoro acetic acid
is sufficiently strong.
OH OH
H2O2 NaOH
HCO2H H2O, 45 oC
40-45 oC OCHO OH

Similar results also obtained from trifluoroacetic acid.

H CF3CO3H C10H21 C CH HCl n-C10H21 C CH

n-C10H21 C CH2
(C2H5)3NHCF3CO2- MeOH
CF3COOH, CH2Cl2 OH OCOCF3 Reflux OH OH

However, the use of perbenzoic acid or m-chlorobenzoic acid in CHCl3/CH2Cl2 or

perbenzoic aid in ethylacetate, permit the isolation of initially formed epoxide.
H2 H
O-CO-CH C H2 H
C CH3
C O-CO-CH C CH3
O CH3CO3H
O O
CH3CO2C2H5
CH3 40 oC
CH3
Oxidation of Carbonyl compounds (C=O) by Peracid

Although the reaction of ketone with peracids is much slower, the reaction
catalyzed by strong acid or strong peracids convert carbonyl compounds to ester
in good yield. This reaction is known as “Baeyer-Villiger oxidation”.

CH3CO3H
p-O2N-C6H4-CO-C6H5 p-O2N-C6H4-CO-O-C6H5
H2SO4
CH3CO2H
RT
CF3CO3H
COCH3 OCOCH3
CF3CO2H
Na3PO4
CH2Cl2, reflux

If the strong peracid is used, a buffer such as solid sodium phosphate is used to
minimize the trans esterification of peroxytrifluoroacetic acid.

CH3CO2C2H5 + CF3CO2H CF3CO2C2H5 + + CH3CO2H

Oxidation of Carbonyl compounds (C=O) by Peracid
The oxidation of cyclic ketone with peraids provide the useful route for the
preparation of lactone.
O O

CF3CO3H O
CF3CO2H
10-15 oC

O O

C6H5CO3H O

CHCl3
RT

For seven and eight member ring elevated temperature is required and the
substantial amount of dicarboxylic acid is obtained.
O
O

C 6H 5C O 3H O + H O O C -( C H 2 )4 -C O O H
C H C l3
RT 33%
29%
Mechanism

OH O H
H+
R 2 C=O + CH 3 CO 3 H R C O O C CH 3 R C OR
+
R O CH 3 COOH
O
H+
R C OR

The reaction is catalyzed by acid and the oxidation accelerated by the presence
of electron donating group in ketone.
The relative ease of migration t-alkyl> cyclohexyl> sec-alkyl~ phenyl~benzyl>
cyclopropyl> methyl.

O
O
C6H5CO3H
COCH3
O CHCl3, RT OCOCH3
H
H

retention of configuration
Oxidation with Periodic Acids
Aqueous solution of periodic acid serves as remarkable selective reagents for the
free cleavage of 1,2 diols and relative compounds such as 1-amino-2-hydroxyl
compounds, 1,2-diketones

Periodic acids exits in two forms; orthoperiodic acid and metsaaperiodic acid.
O O
HO OH
I I
HO OH O O
OH OH
(H 5IO 6) (H IO 4)
Orthoperiodic acid Metaperiodic acid

The frequently used reagents are NaIO4/KIO4, sodium or potassium

metaperiodic acid.

The main advantages of using periodic acid in the diol cleavage is the use of
water as solvent. For water insoluble organic compounds, Pb(OCOCH3)4 is more
suitable reagent.
Oxidation with Periodic Acids
Like Pb(OCOCH3)4, the oxidative cleavage of 1,2-diols also involves the formation
of cyclic intermediate. The cleavage of 1,2-diols is usually most rapid in the acidity
range pH 1-6 where the monoanion of paraperiodic acid seems principle reagent.

KIO4
H H2SO4 H
H3C(H2C)7 C CH (CH2)7CO2H H3C(H2C)7 C CH (CH2)7CO2H
H2O, C2H5OH
OH OH 40oC O O

I
O O
HO OH

-IO3
-H2O

CH3(CH2)7CHO + CHO(CH2)7COOH

Since, periodic acid oxidation involves the formation of cyclic intermediate, the
diol which can form cyclic intermediate easily oxidize more rapidly than other
isomer.
Oxidation with Periodic Acids

For example, the oxidation of racemic 2,3-butanediol oxidize more rapidly than
the oxidation of mesoisomer.
H
H
H 3C
OH
H 3C H 4IO 6 H 3C
O O
H 3C Products
H OH
OH I
H O OH
O
H3C H 3C

H H
OH O O
H 3C H 4IO 6 H3C
OH Products
I
H H O OH
OH
O

The cyclic intermediate from the racemic-diol has less non bonded interaction
between the methyl group than meso-isomer
Oxidation with Periodic Acids
Similarly, cis-1,2 cyclohexanediol oxidize more rapidly than trans-1,2
cyclohexanediol.
H
H

OH H4IO6 O
O OH
OH Product
O I
OH
H
H O
cis-

H H

H4IO6 O
OH O
H
OH Product
H I
O OH
HO O
trans-
More puckered

The cyclic intermediate from trans-1,2 cyclohexanediol is less favorable because

of increased puckering of the six member ring.
Oxidation with Periodic Acids
The oxidative cleavage of 1,2-diketone is also believed to involves the formation
of cyclic intermediate prior to cleavage.

CH3 CH3 O
CH3 O

O C KIO4 O C O I (OH)4
HO C O I (OH)3
CH3COOH
O C H2O, 0 or 22 oC O C H-transfer O C O

CH3 CH3 CH3

CH3
O
HO C O OH
I OH 2CH3COOH
HO C
O OH
CH3
Oxidation with Periodic Acids
The oxidation reaction of 1-amino-2-hydroxyl compounds also proceeded through
the formation of cyclic intermediate.

OH
N a IO 4
O H2 H2
H aN C O 3 C
O 2N CH C C OCH3 O 2N CH C OCH3
H 2O , C 2H 5O H
NH2 25 oC HN O
I O
O
HO OH

O 2N C NH + H O 2C OCH3
H

H 2O

O 2N CHO