Dr. M.

Athar Abbasi

OXIDATION
The term ‘oxidation' can be defined in different ways:-
1) Addition of oxygen to the substrate e.g.

[O]
C C C C An epoxide
or Oxirane
An alkene O

2) Removal of hydrogen from a molecule i.e.

OH O

C C R C C R
[ H2 ]
H

3) The loss of electrons by an atom or an ion and increase in oxidation state is called
oxidation.
O O

e
Phenoxide anion Phenoxide radical

e e
Cu0 Cu 1+ Cu 2+
2e
Zn0 Z n2+

Gain of electrons by an atom or ion and decrease in oxidation state is called reduction.
e
Cl Cl
e 2e
Fe3+ Fe2+ Fe0

4) Oxidation is conversion of functional group from lower category to higher category.

Reduction is conversion of functional group from higher category to lower category.

[O ] [O] [O]
R CH3 R CH2 OH R CH O R COOH
Oxidation

Reduction

 OXIDATION STATE
There is a simple rule for knowing the oxidation state of an atom in a molecule or
overall oxidation state of a molecule. Neutral atom of the element has an oxidation state
of zero. Oxidation numbers of certain atoms are given below.

1
 Dr. M. Athar Abbasi

No. Atom Oxidation State

1. -H (C-H) +1
2. =O (C=O) -2
3. -O (C-O-) -1
N -3
4. =N -2
-N -1
5. Halogens (C-X) -1
(C-C) 0
6. (O-O) 0
(N-N) 0

The oxidation state for any single carbon atom in a molecule is obtained by
counter-adding the values given in the above table for its four bonds. Each carbon in a
molecule can be labeled with its oxidation state and sum of these oxidation states in a
molecule may be compared to the sum of other molecule in any reaction to know that
whether overall oxidation state was increased or decreased.
 If the oxidation state changes from negative to positive then it is oxidation.
 If the oxidation state changes from positive to negative then it is reduction.
 If the oxidation state remains same or there is no change in the oxidation state
then it is neither oxidation nor reduction as in the case of hydration of ,-
unsaturated aldehyde.
(in the presence of H2SO4)
O OH O
H2O
H3C CH CH C H H3C CH C H2 C H
H2O
Oxidation states of carbons -3 -1 -1 +1 -3 0 -2 +1
Overall oxidation state -4 -4

Examples:
+1 +1
H H
+1 H H +1
+1 +1
i) H C C H = -6 ii) C C = -4
+1
H
H H +1 -3 +1 H
-3 +1
-2 -2
H +1
+1 +1 +1 +1
iii) iv)
H C C H = -2 H C H = -4
-1 -1 H -4
+1
O -2 O -2
+1 +1 +1 -1
v) H C H = 0 vi) H C OH = +2
0 +2

2
 Dr. M. Athar Abbasi

-1 Cl
-2 -2 -1 -1
vii) O C O = +4 viii) Cl C Cl = +4
+4 -1 Cl +4
+1
H O
+1 -3
ix) H
H C C N = 0 x) H C C N C CH 2 Cl = -2
+3 -1 +1 +3 -1
-3 H
+1
H +1
+1 -1
H C OH O
C -1
xi) -1 +1 C = 0 xii) H3C CH 2 C NH2 = -2
+1 +1 0 +1
C C -3 -2 +3
H N H

CH 4 CH 3OH So it is oxidation.
-4 -2
HO H O

-2 0 -2 -2 +2 -2
So it is oxidation.
-2 -2 -2 -2 -2 -2

= - 10 = - 08
O O
3Br2
H3C C CH 3 H3C C CBr 3 So it is oxidation.
-3 +2 -3 NaOH -3 +2 +3

= -4 = +2
Ph Ph Ph
+
H
Ph C C Ph Ph C C Ph Intramolecular
oxidation-reduction
+1 OH OH +1 +2 O Ph 0

= +2 = +2
O

H C C H H3C C H Neither oxidation nor reduction.

-1 -1 -3 +1
= -2 = -2
O
2H2O
CH2Cl2 CH 2-( OH)2 H C H
0 - H2O
0 0
Apparently it is oxidation but neither is it oxidation nor reduction.
O OH
HO
H 2O
Neither oxidation nor reduction.
Br CH2 CH CH 2 Br CH 2 CH CH2
-1 0 -1 -1 0 -1
= -2
= -2

3
 Dr. M. Athar Abbasi

Categories of simple Functional Groups arranged according to oxidation state.

Approximate oxidation numbers of carbons in various molecules are:
-4 -3 -2 -1 0 +1 +2 +3 +4
CH4 CH3 H H RCH2Cl O O O O CO2
etc C C etc. CCl4
H C H R C H R C R R C OH
H H
H3C-R CH2Cl R3C-OH O O CF4
CH3OH
etc. C (Solid) etc. H C OH R C NH 2 etc.
CH3Cl
CH3NH2 CHCl3 etc.
etc.
Oxidation

Reduction

 OXIDATION OF HYDROCARBONS
Oxidation of following types of hydrocarbons will be taken into account.
A) Olefins
B) Aromatic rings
C) Saturated C-H groups

A) OXIDATION OF OLEFINS
Oxidation of olefins is mostly carried out via:
1) Epoxidation
2) Diol formation
3) Cleavage of the double bond

1) EPOXIDATION
The reaction of olefins with peracids to form epoxides is known as Epoxidation. It
provides a selective and convenient method for the oxidation of carbon-carbon double
bonds (C=C). Olefins may be epoxidated with a number of peracids:

O
O
Performic acid Peracetic acid H3C C O OH
H C O OH
O
O
C OH
O
Perbenzoic acid C O OH Monoperphthalic
acid OH
O C

C OH O O
O
m-Chloroperbenzoic Trifluorperacetic F3C C O OH
acid (MCPBA) acid
O
Cl
Caro's acid/persulfuric HO S O OH
acid
O

Peracids are prepared by the reaction of acids with peroxides.

4
 Dr. M. Athar Abbasi

O O
H+
H3C C OH + H2O2 H3C C O OH + H2O
Mechanism:-
O O H O H
HO OH
H+
H3C C OH H3C C OH H3C C OH

O H O H O OH
+
H
H3C C OH H3C C O OH
H2O
Peracetic acid
O OH

Epoxidation of olefins with peracids takes place as under.

O O O
H H H H
+ R3 C O OH + R3 C OH
R1 R2 R1 R2
Mechanism:- The process involves electrophilic attach on the olefin and a simplified
representation is as:
O
R2 O R1 R2 R1 R2
R1 R2
O C R3 R1 +
H
+ HO O C R3
H H H H H O H H O H
O
H H
Consequently, electron-releasing groups in the olefin and electron-attracting
group in the peracid facilitate the reaction. In fact the two steps are closely synchronous,
(simultaneous), so that a truer representation is:
H
R3 H R3 R1
R1 H O R1 O R3
C C C C O
C C
O O O +
+
C H O C H O C OH
R2 R2 H R2
H
H

Stereochemistry:-
Epoxide formation is stereospecific, ‘cis’. Thus cis-2-butene on reaction with
peracid gives only the cis product.
H O O
H H H O
+ H C O OH + H C OH
H3C CH3 H3C CH3
In reaction with cyclic olefins, the approach of the peracid is predominantly from
the less hindered side, e.g.
CH3 O CH 3
O O
+ H3C C O OH + H3C C OH

H H

5
 Dr. M. Athar Abbasi

When a strong acid such as performic acid or trifluoroperacetic acid is used, the
carboxylic acid produced is sufficiently acidic to bring about the ring-opening of the
epoxide with the production of a diol-monoester. Reaction occurs by SN2 displacement
on the protonated expoxide and the nucleophile attacks the less alkylated carbon e.g.
H
HO
O O
F3CCO2OH F3C CO2H H3C CH C H2
H3C CH C H2 H3C C H C H2 H3C CH CH2
F3CCO2H OO C C F3 OOCCF3

Peracetic acid being a weaker acid requires elevated temperatures. Ring-opening

may be prevented by carrying the epoxidation in a suitably buffered medium.

Uses of Epoxides:-
Epoxides have four uses in synthesis.
i) Reduction gives an alcohol.
O HO
L iAlH4
H3C CH CH 2 H3C CH CH 3
ii) Treatment with a Lewis acid gives a carbonyl compound.
BF 3
O BF 3 O BF 3 O
O O
BF 3
H3C CH CH 2 H3C CH CH H3C CH2 CH H3C CH2 CH H3C CH2 C H
BF 3
H
iii) Treatment with dimethyl sulphoxide (DMSO) gives a -ketol.
CH3
O S
O
CH 3 CH3
R CH CH R' R CH C R'
+ O S R CH C R'
CH 3 S(CH3)2
O O H OH

iv) When oxirane (epoxide) reacts with water in the presence of catalytic amount of acid
or base, ring opening takes place to afford vicinal diol. This is well known fact that
the epoxide ring opening always takes place in trans manner so we will get an anti
diol product.

H HO H
H3C 1) MCPBA
CH3
C C C C
H3C
+ OH
H CH3 2) H , H2O H
trans-2-butene meso-2,3-butanediol
H H OH
H H 1) MCPBA HO
C H3 H3C
C C C C C C
H R
+ S
H
CH 3
+
2) H , H2O R OH S
H3C H3C HO CH3
cis-2-butene (2R, 3R)-2,3-butanediol (2S, 3S)-2,3-butanediol

6
 Dr. M. Athar Abbasi

Other nucleophiles also cleave the epoxide ring, reacting preferably at the less
substituted carbon atoms e.g.
O OH Br
Br
H3C CH CH 2 H3C CH CH 2 + H3C CH CH 2

76 % Br 24 % OH
The ring-opening of epoxides of rigid cyclohexene systems gives trans-diaxial
products.
OH
HO H2O

O OH

2) DIOL FORMATION
Following reagents are mostly used for converting olefins directly into diols.
(i) Osmium tetroxide (OsO4) or KMnO4
(ii) Iodine-silver carboxylates (Dry & Wet methods)

(i) Osmium tetroxide (OsO4)

The addition of an olefin to OsO4 in ether causes the rapid precipitation of a
cyclic osmate ester. Pyridine which complexes the osmium atom in the ester, is often
added as a catalyst. Then ester is hydrolyzed, commonly with aqueous sodium sulphite to
give a cis-1,2-diol.
H H H
R R R
C O O C O O C OH HO O
H2O
+ Os Os + Os
C ether C Na 2SO 3 C OH O
O O O O HO
R H R R
H H
OsO4 is both highly toxic and expensive but is valuable reagent because of its
specificity for olefinic bonds and the ease of its application. It gives better yields than
KMnO4. Strained and unhindered olefins react rapidly.
C H3
CH3
OH
OsO4
70 %
OH
CH3
C H3
This reagent attacks rigid cyclic systems from the less hindered side.
CH3
CH 3
CH 3
H2O HO
OsO 4

O
OH
O
Os O

7
 Dr. M. Athar Abbasi

Catalytic amount of OsO4 with less expensive oxidants also works well.
H H
R R
C OsO 4 C OH
+ OsO 4
C H 2O 2 C OH
R H R
H
Potassium permanganate (KMnO4)
Oxidation with KMnO4 is widely used method for cis-perhydroxylation of
alkenes, but needs careful control to avoid over-oxidation. Best results are obtained in
alkaline solution, using water or aqueous organic solvents (acetone, ethanol or t-butanol).
In acid or neutral solution, -ketols or even cleavage products are formed.
H H
R R H
KMnO 4 KMnO 4 R
C OH C
(CH3)3C-OH (CH3)3C-OH C OH

C O C NaOH
R C OH
id R H
ac R H
2 C O
Mechanism:-
H H H H
R R R R
O O O O
C C NaOH C OH H2O C OH
+ Mn Mn
C C O H2O C
O O O O C OH
R H O
R H R R H
[Mn (VII)] [Mn (V)] H Mn
[ Mn (V)] O O
H MnO 4
R H H
C O O O R
R
O C OH
Mn C Mn
C O O O H2O
H2O C O C O
R [Mn (VI)] [Mn (IV)] R
H R

These reactions are believed to proceed through the formation of cyclic

manganese esters and it is this which controls the cis (syn) addition of the two hydroxyl
groups. In acid solution cleavage of the double bond may occur.
OH KMnO4 OH
O H Ol eic H HO
KMnO4 NaOH (Excess)
H3C- (H2C) 7 CH C C C C C H
H 2O H 2O H
H3C -(H2C)7 Acid (CH2)7C OOH H3C-(H2C )7
75 % (CH2)7COOH (CH2)7COOH
81%

CH O OH
KMnO 4, MgSO KMnO 4, NaOH
4 H
HO
o
H2O, t-Bu-OH, 0 C
H2O, AcOH, - 15 o
C H
54-66 % CHO Norbornene 40 %

8
 Dr. M. Athar Abbasi

(ii) Iodine and Silver carboxylates

Many of the difficulties attending the oxidation of alkenes to 1,2-glycols with
other reagents can be avoided by using Prévost’s reagents – a solution of iodine in carbon
tetrachloride together with an equivalent of silver acetate or silver benzoate. Under
anhydrous conditions this oxidant directly yields the diacyl derivates of the trans-glycol
(Prévost’s conditions), while in presence of water the monoester of the cis-glycol is
obtained (Woodward conditions). The hydrolysis of these will result in respective diols.

Ac O o us Ac O OH
Anhy dr H2O
C C C C C C
Conditions +
OAc
I2 , CCl4 , AgOAc CH3
Mechanism:- O C
O
O C O
C C AgI
O CH3
C C C C C
I I Ag O C H3
I I
ium ion
Iodon
CH3 CH3
C C AcO ost's
Ag O O O O (Prev
C C method)
O
AgI C C C C OAc
C
O CH3 Diacety l t rans-diol
H3C O H
H2O C Ac O OH
O Proton Monoacety l c is-diol
O C C
Shif t ward's method)
C C (W ood

The value of this reagent is due to its specificity and the mildness of the reaction
conditions. Free iodine, under these conditions used, hardly affects other sensitive groups
present in the molecule.

3) CLEAVAGE OF THE DOUBLE BOND

The complete oxidative cleavage of alkenes can be carried out via.
(i) Ozonolysis
(ii) Lemieux reagent (NaIO4)
(iii) Chromium (IV) oxide (e.g. CrO3, CrO2Cl2, H2CrO4 etc.)

(i) Ozonolysis
The reaction of ozone with olefin is called ozonolysis. It is the most general and
mildest method of oxidatively cleaving alkenes to carbonyl compounds. The alkene is
treated with ozone at low temperature in solvent like methanol, ethyl acetate or CH2Cl2.
Ozone reacts as an electrophile with olefins, forming a primary ozonide (molozonide)
which rearranges through a zwitterionic intermediate to an isolable ozonide. The ozonide
is reduced to the two carbonyl products by different treatments like catalytic
hydrogenation, Zn/AcOH or by reaction with DMSO. Resonating structures of ozone are:

9
 Dr. M. Athar Abbasi

O O O
O O O O O O

O O
O3 Reduction
C C C O + O C
solvent
O
Mechanism:- Ozonide

O O
C C C C O
O
+ C O +
O O C
O O O
O
O
A molozonide Ozonide
H2 / Pt
H (CH3)2S
O
Ac
Z n/
2 C O + H2O 2 C O + Z nO 2 C O + (C H3)2SO

Ozonides are dangerously explosive, however usually converted at once into

products.
Et Me 1. O3, CH2Cl 2 Et Me
C C C O + C O
Me H 2. Zn/AcOH Me H
C H3
CH3
1. O 3, CH2Cl2
HO
2. Zn/AcOH
O

CH2 O
CH3 CH3
O
1. O3, MeOH
+ C
H H
2. (CH 3)2S

Reaction with dimethyl sulfide has been found to give excellent results and this
reagent appears to be superior to others mentioned. Reaction takes place under neutral
conditions and the reagent is highly selective as nitro or carbonyl compounds present
elsewhere in the molecule are not affected.
Direct solvolysis (in the absence of reducing agent) gives ketones and/ or acids,
depending on the structure of the olefin e.g.

R R' O O O OH
O3 R H2O R
R'
C C
solvent C O + R' C H
R H H
R O R
Ozonide OH
O Hy droperoxy compd.
H2O
R' C OH

10
 Dr. M. Athar Abbasi

Treatment of the ozonide with NaBH4 leads to alcohols. In this way a double
bond can be oxidatively cleaved to produce two alcohols.
1. O3, CH2Cl2
H3C-H 2C-H 2C-HC CH-CH 2-CH 2-CH 3 2 CH 3-CH 2-CH 2-CH 2-OH
2. N aBH4 / MeOH
O O
1. O 3, C H2C l2
CH 3-CH=CH-(CH 2)7-C OMe CH 3-CH 2-OH + HO-CH 2-(CH 2)7-C OMe
2. N aBH4 / MeOH

(ii) The Lemieux Reagent (NaIO4)

Ozone is unpleasant to handle and is not selective for olefins, e.g. secondary
alcohols may be oxidized to ketones and tertiary C-H bonds to alcohols. Ozone has
therefore largely been displaced by the Lemieux reagent which is selective for olefins.
Lemieux reagent consists of dilute aqueous solutions of sodium periodate + catalytic
quantity of KMnO4 or of OsO4. In each case, the olefin is first oxidized to the cis-diol
which is then cleaved by periodate to give aldehydes and/or ketone. The permanganate
reagent then oxidizes aldehydic products to carboxylic acids. However, the combination
of periodate and OsO4 has the advantage that the reaction does not proceed beyond the
aldehyde stage.
Me Me Me Me
NaIO 4
C C C O + C O
H KMnO 4 Me
Me HO
The mechanism involves the formation of a diol followed by the reaction with NaIO4.
Me
C O
Me Me Me Me HO
Me Me Me H Me C C
H Me Me KMnO 4
KMnO 4 C C
C C C O + C O
or OsO 4 OH OH O O
Me H Me H
O O HO I OH +

I O O HO O H
O I
O O H2O
O I O O

O
Reaction is conducted at pH 7-8. The permanganate is reduced only to the
manganate stage at this pH and is re-oxidized by periodate, which itself does not attack
the double bond. Only catalytic amounts of permanganate are thus needed. Citronellal,
with this reagent, is oxidized to acetone and 3-methyladipic acid in high yields.
CH3 CH3

O
N aI O4, KMnO 4
C HO +
COOH
H2O, (CH3)3C -OH H3C CH3
COOH

H3C CH3

11
 Dr. M. Athar Abbasi

(iii) Chromium (VI) Oxide

CrO3, CrO2Cl2, and H2CrO4 can be used for such oxidation.
a) With CrO3
The cleavage of olefinic bonds with chromic oxide is competitive with oxidation of
allylic C-H bonds, e.g. cyclohexene gives a mixture of 3-cyclohexenone and adipic acid.

H H O

CrO3 CO OH
+
COOH

There are two possibilities:

 Partially aqueous medium favours the cleavage process.
 Anhydrous medium such as glacial acetic acid/anhydride favours allylic oxidation.
O H H

CrO 3 Aq. CrO 3 COOH

Acetic COOH
anhydride
In many allylic oxidations, the double bond is found in a position indicating that
an allylic transposition occurs during the oxidation.
C H3 CH3

CrO3-pyridine

CH2Cl2
O
Detailed mechanistic understanding of the allylic oxidation has not been
developed. One possibility is that an intermediate oxidation state of Cr, specifically
Cr(IV), acts as the key reagent by abstracting hydrogen.
CH 3 H3C H CH 3 CH 3
O O
OH
+ Cr O Cr O O Cr
O O Cr(OH) 2
O O
H

b) With CrO2Cl2
H
C H2 O H O
O Cl H C Cl
CH2Cl2 C O
+ Cr Cr +
C
0-5 oC C
O Cl CH Cr
Ph Me O Cl Ph Ph Me Cl Cl
Me Or
H
H O C l - CrCl O O
C 2
Cr C + C
C Ph Me H H
O Cl
Ph
Me

12
 Dr. M. Athar Abbasi

c) With H2CrO4
Various products with rearranged carbon skeleton have been isolated from
chromic acid oxidation.
CH 3

O C
R R OH R R O
- OH O
C C + Cr C C R HOOCCH 3
R
OH R
R
R
O OH R - H+ R C C OH
O Cr
(- H2O) R
H2O O Cr
- H+ O
- HCrO3 O
HO R
R
R C C OH CH 3
R
O O Cr C
- H2CrO3 H2O O O
O HO OH
C C R
R
R R R C C R C C R
R
R R
H2CrO 4 R R
O O - H+
- 2H2O
R Cr
O CH 2
2 C O O O
C C
R - CrO2
R C C R O O H2CrO4 O O
R R
C C C C R
R R R
R R R R

B) OXIDATION OF AROMATIC RINGS

Aromatic rings may be:
1) Unsubstituted
2) Substituted

1) OXIDATION OF UNSUBSTITUTED AROMATIC RINGS

The oxidation of unsubstituted aromatic rings, which results in the loss of the
associated stabilization energy, requires vigorous conditions. These drastic conditions are
due to the loss of aromaticity. Resonance can result either in the cleavage of the ring or in
the formation of quinones.
Oxidation of unsubstituted Ar-rings can be carried out with following reagents.
(i) Ozone/solvent & H2O
(ii) O2/V2O5 at 400-500 °C.
(iii) Chromium (IV) oxide (CrO3)

(i) Ozone/solvent & H2O

Direct solvolysis with ozone affects cleavage e.g.
C OOH
O3 / solvent
Phthalic acid
H2O 88%
COOH

13
 Dr. M. Athar Abbasi

Diphenic acid
65%

O3 / solv ent

H2O COOH
COOH

(ii) O2/V2O5 at 400-500 °C

An industrial method, which is cheaper one, employs aerial oxidation over a
vanadium pentoxide catalyst at 400-500 °C.
O
O2/ V2O5
O Maleic anhdride
400-500 oC
O
O
O2/ V2O5
O
400-500 oC

Phthalic anhdride O

This method is particularly important since some of the derived diesters e.g.
dinonyl phthalate, are used as plasticizers for cellulose acetate and polyvinyl chloride.
Polyesters resins and phthalocyanine dyes are also manufactured from phthalic
anhydride.

(iii) Chromium (VI) Oxide (CrO3)

Aq. CrO3 can also be used for oxidative cleavage e.g.

O Py ridine-2,3-dicar- O
boxylic acid
Aq. CrO 3 HO HO

H O CO2
N N N
O Nicotinic acid

CrO3 in anhydrous medium does not lead to ring fission. Mechanism is not clear yet.

O
20%

CrO 3

AcOH
25 oC
1,4-Naphtha-
quinone O

14
 Dr. M. Athar Abbasi

2) OXIDATION OF SUBSTITUTED AROMATIC RINGS

Oxidation of phenols and aromatic amines will be discussed hereby as examples
of substituted aromatic rings.

(i) Oxidation of Phenols

The aromatic rings of phenols are very susceptible to oxidation by one-electron
oxidants. The removal of hydrogen radical from a phenol gives a delocalized aryloxy
radical. The coupling of these radicals may take place at ortho-ortho, para-para, or
ortho-para positions depending upon the structure of the phenols.

OH O

+
Fe3
+ H

H
O O O O O

F e3+

O O O O OH HO
HH

Thus - and -naphthols undergo oxidative coupling in the presence of excess of

FeCl3.

OH
FeCl 3
(excess) OH
Binaphthol
2H OH

H3C CH3 H3C CH3

H3C
Fe 3+ Fe 3+
2 H O O H O O
HO 2H
2H
CH 3 H3C CH 3 H3C CH 3

Cyclization to derivatives of dibenzofuran can arise through intramolecular

nucleophilic attack on intermediate quinone. For example, the oxidation p-cresol by
hexacyanoferrate (III) ion gives in addition to carbon-carbon dimmers, the Pummerer’s
ketone.

15
 Dr. M. Athar Abbasi

OH
O
3 O
[Fe(CN) 6]

Mechanism: H3C
H3C
CH3 Pummerer'sketone
H
O O O O O

Fe 3+

CH 3 CH 3 CH 3 CH3 CH 3

O O O O O
OH

H
+
H3C H3C H3C
H3C H3C H3C

O O

O
Proton O H Taut.
Shift
H3C H3C
H3C H3C Pummerer'sketone

(ii) Oxidation of Aromatic Amines

Chromic acid can be used for the oxidation of aromatic amines.
NH 2 O

Na 2Cr 2O7

H2SO 4
nims:
Mecha
O
Na 2Cr 2O7 + H2SO 4 + H2O Na 2SO 4 + 2H 2CrO 4
O
NH2 NH3 O Cr OH
O
O
O
+ HO Cr OH
+ O Cr OH
NH 3
O
O
H
O
O O O
O Cr OH
H2CrO 3 HO Cr OH
O
O
O
H2Cr O3
O HO Cr O +
H O Cr OH
O O

16
 Dr. M. Athar Abbasi

The aminophenols can also be oxidized by one-electron oxidants.

NH2 O
OH O
+
Fe 3

Mechanism:
H H
NH 2 N NH
O
O H O O
O
Fe 3+ H+

H H2O
H

C) OXIDATION OF SATURATED “C-H” GROUPS

Following systems will be considered.
1) Allylic and benzylic systems
2) Active methylenes
3) Unactivated C-H groups
4) Aromatization

1) OXIDATION OF ALLYLIC AND BENZYLIC SYSTEMS

The comparative stability of allyl and benzyl radicals renders allylic and benzylic
systems susceptible to oxidation via free radical reactions.

H2C CH CH2 H2C CH C H2

CH2 CH2 CH2 CH2 CH2

The chlorination of toluene in the vapour phase or under reflux gives benzyl
chloride, benzal chloride and benzotrichloride from which benzyl alcohol, benzaldehyde
and benzoic acid, respectively, are formed on hydrolysis.
CH3 C H2Cl CHCl2 CCl3

Cl2 -Vap.
+ +

Benzyl chloride Benzal chloride Benzotrichloride

OH H2O OH H2O OH H2O

CH2OH CHO COOH

17
 Dr. M. Athar Abbasi

Mechanism involves free radicals.

H Cl Cl 2Cl

H C H CH 2 CH 2Cl CH 2OH
+ Cl
Cl OH

HCl H2O

Cl C H Cl CH CHCl 2 CHO
+ Cl
Cl OH

HCl H2O

Cl

Cl C H Cl C Cl CCl 3 COOH
+ Cl
Cl OH

HCl H2O

The alcohol and aldehyde are produced in this way on an industrial scale.
However, this method results the formation of many products which cause difficulty for
separating the halogenated products. Mono-halogenated product may be obtained by
using sulphuryl chloride (SO2Cl2) in the presence of peroxide. e.g. toluene gives benzyl
chloride in 80% yield.
C H3 C H2C l C H2O H

SO 2C l2 OH
80%
Peroxide H2O

Mec hanism:- O
O O
Dibenzoylperoxide
initiates the reaction. 2 O C Ph
Ph C O O C Ph
H
O
SO 2 + Cl
H C H O C H2 CH2Cl
Cl S Cl
O
O C Ph
O
+ S Cl
Ph-COOH
O
H

H C H CH2 CH2Cl CH2OH

+ Cl
Cl OH

H Cl H2O

18
 Dr. M. Athar Abbasi

The oxidation of allylic and benzylic systems can be carried out to either –COOH
group or up to aldehydic level.

o Oxidation to –COOH Group

Reagents used are KMnO4 or conc. HNO3. Aerial oxidation can also be affected.
Dilute permanganate oxidizes o-chlortoluene to o-chlorobenzoic acid in about 65% yield.

C H3 COOH
Cl Cl
KMnO 4

Conc. HNO3 oxidizes o-xylene to o-toluic acid in 54% yield.

CH3 COOH
CH3 CH3
Conc. HNO3

Substituents on the methyl group are also removed in these conditions e.g.
Nicotine
Nicotinic acid
COOH
N Conc. HNO 3

C H3 70 oC
N N
Industrially benzoic acid is manufactured by the catalytic air oxidation of toluene.
C H3 COOH

Aerial oxidation

o Oxidation to Aldehydic Level

Commercially, a particularly important example is the oxidation of propylene to
acrolein over copper (II) oxide at 300-400 °C.

CuO
H2C CH CH 3 H2C CH CHO
o
300-400 C
In the laboratory, following are the three reagents which are mostly used for the
selective oxidation of Ar-CH3 to Ar-CHO.

(i) Chromyl chloride (CrO2Cl2) in CCl4 or CS2, (Etard reaction)

(ii) Chromium oxide (CrO3) in acetic anhydride
(iii) p-Nitroso-N,N-dimethylaniline

These three methods are discussed hereby.

19
 Dr. M. Athar Abbasi

(i) Chromyl chloride (CrO2Cl2) in CCl4 or CS2, (Etard’s reaction)

The Étard’s reaction is a chemical reaction that involves the direct oxidation of
an aromatic or heterocyclic bound methyl group to an aldehyde using chromyl chloride. It
is named for the French chemist Alexandre Léon Étard.

CH 3 CHO

CrO2Cl 2

CS 2
nism:-
Mecha H O Cl
CH 2 H CH 2 O C Cr CHO
O Cl [2,3]-sigmatropic H
Cl ene Cl
Cr HO
Cr ion angement
+ react Cl rearr
HO
O Cl
HCl
HO Cr Cl

The reaction mechanism proceeds via an ene reaction with chromyl chloride,
forming the precipitated Étard complex. The Étard complex is then decomposed by a
[2,3]-sigmatropic rearrangement under reducing conditions to prevent further oxidation to
a carboxylic acid. Reducing conditions for the decomposition of the Étard complex are
provided by saturated aqueous sodium sulphite. Typical solvents for the reaction
include carbon disulfide, chloroform, and carbon tetrachloride, with carbon tetrachloride
being the most common. To obtain a highly purified aldehyde product, the Étard complex
precipitate is often purified before decomposition in order to prevent reaction with any
unreacted reagent. The reaction is normally carried out for a few days to several weeks
and the yields are high.

(ii) Chromium oxide in acetic anhydride

Benzaldehyde can be obtained by the oxidation of toluene with chromic oxide in
acetic anhydride. In this reaction benzaldehyde formed is trapped by acetic anhydride to
form benzal diacetate. As a result, further oxidation of benzaldehyde to benzoic acid is
prevented. However, benzaldehyde is regenerated by the hydrolysis of benzal diacetate.

H3C O C O OC OCH3
CH3 CH CH O

CrO3 H2O
+ 2 CH3CO OH
(CH3CO)2O

Mechanism:- H O OH
C Cr CH O
CH2 H CH2 O
H
O OH [2,3]-sigmatropic
ene O
Cr
Cr O r earrangement
+ reaction O
O Cr (OH)2

20
 Dr. M. Athar Abbasi

O O O O

H 3C C O C CH3 H 3C C O + C CH3

O OCOCH
H 3
H3COCO OCOCH 3
C O HC
CH
O
H3C C O
+ C CH 3

HO OH CHO
H2O CH

- 2CH 3COOH H2O

(iii) p-Nitroso-N,N-dimethylaniline
The benzylic compound is treated with p-nitroso-N,N-dimethylaniline and the
resulting schiff base is hydrolyzed. The method is applicable only to those compounds
whose methyl groups are strongly activated, e.g. 2,4-dinitrotoluene.

O
CH 3 N CH O NH 2

NO2 NO2

+ +
solvent

NO 2 N NO 2 N
H3C CH3 H3C CH 3
Mechanism:-
O CH 3
H H3C CH 3 O H
CH2 N CH 2 N CH2 N N
CH 3
NO 2 NO2 NO 2

+ Proton
+
shift
NO2 N NO 2 N NO2
O H3C CH 3
H
H OH CH3 Schiff base CH3
N H2
CH N N CH N N CHO
CH3 CH3
NO2 NO2 NO2

+
H2O H+/H 2O
N
NO 2 NO 2 NO 2 H3C CH3

21
 Dr. M. Athar Abbasi

2) OXIDATION OF ACTIVE METHYLENES

Methylene groups adjacent to carbonyl group (−CH2−CO−) may themselves be
oxidized to carbonyl in two ways:
(i) Thorough oxime formation
(ii) By selenium oxide (Riley reaction)
Both methods are discussed hereby.
(i) Through Oxime Formation
The methylene (−CH2−) group is activated by the adjacent carbonyl group
towards reaction with organic nitrites in the presence of acid or base. The resulting
nitroso compound tautomerizes to the oxime, which may be hydrolyzed to the respective
-dicarbonyl compound.
O R O R O
O O
R-ON
O Pr oton
R CH2 C R H C C R C C R R C C R
:- H+/OH shift OH /H 2O
nism +
Mecha N O N OH H2N OH
O R O R O
O
H2O [H 2O]
R CH C R
R CH C R H C C R H C C R
]
H OH R O N O [- R OH
RO N O -
[- OH ] N O
O
n O O
Pr oto
R C C R
shift
R C C R + H2N OH
OH /H 2O
N OH
(ii) By Selenium Dioxide (Riley reaction)
The reaction occurs through the enolic form of the carbonyl compound. SeO2 is
white crystalline solid and poisonous. Usually it is used in the form of solution in acetic
acid or acetic anhydride or ethanol or water or dioxane.
O SeO 2 O O
H2O, AcOH
Ph C CH 2 Ph Ph C C Ph
69 oC
There are two possible mechanisms.
I. In aqueous ethanolic solution, SeO2 forms selenic acid i.e. H2SeO3. The enolic form
of the substrate then attacks on the H2SeO3.
O
Et-OH
O Se O + H2O Se
HO OH
O
OH HO
Se
OH Se Se
HO H+ HO O H H2O O
O + O O

Ph C CH Ph Ph C CH Ph Ph C CH Ph

H Se
O O OH O O
0
Ph C C Ph
Ph C C Ph + Se
H2O
H

22
 Dr. M. Athar Abbasi

II. In the presence of acetic anhydride, electrophilic attack on the SeO2 takes place by
enolic form of the ketone.

O
HO
Se
O Se
+ O Se
O H O O O OH O O
0
Se
Ph C CH Ph Ph C CH Ph Ph C C Ph Ph C C Ph
H2O
H
Camphor reacts under refluxing condition in acetic anhydride to give camphor
quinone in 95% yield.
CH3 C H3
H3C H3C
CH3 CH3
O O
SeO 2

Ac2O

O
Acetophenone reacts in dioxan to give phenylglyoxal in about 70% yield.
O SeO 2 O O
Pheny lgly oxal
Ph C CH 3 O O Ph C C H

In contrast to the oxime method, the SeO2 preferentially oxidizes the methyl
group rather than the methylene (−CH2−) group.
O O O O O
R -ONO/H+ SeO2 / solv ent
H3C C C CH3 H3C H2C C CH3 H3C H2C C C H

3) OXIDATION OF UNACTIVATED C−H GROUPS

The selective oxidation of one unactivated C−H group in a molecule possessing
alternative centers for attack is achieved with a difficulty. Those reagents might be used
with which C−H bonds react essentially. The free radicals are relatively unspecific;
however, selectivity is obtained under special circumstances.

(i) Bromination of Alkanes

Halogenation of alkanes takes place when they react with halogens, usually
chlorine and bromine, either on heating at 250-400 oC, or under the influence of light, to
form haloalkanes. Bromination is similar to chlorination but since bromine is less
reactive than chlorine, it is more selective in the site of attack and mainly attacks the
tertiary hydrogen atom.
CH 3
> 99% CH 3 Traces CH 2Br
h
H 3C C H + Br Br H 3C C Br + H 3C C H
127 oC
CH 3 CH 3 CH 3

23
 Dr. M. Athar Abbasi

M e ch anism :-
CH 3 CH 3 CH 3

H3C C H + Br Br H3C C Br H3C C Br

HB r +
CH 3 CH 3 CH 3
The ration of the relative reactivity of a tertiary, secondary and primary hydrogen
atom towards bromination at 127 oC is 1600:800:01.
The oxidation of tertiary C−H to C−OH can sometimes be achieved directly with
alkaline permanganate. The reaction occurs with retention of configuration.
R R
Alkaline
R' C H C OH
KMnO 4 R'
"R "R
(ii) Photolysis of Nitrite (Barton reaction)
Intramolecular free-radical reactions occur specifically through six-membered
cyclic transition states, so that it is possible to selectively oxidize -CH bonds in a
molecule.
h
H3C C H2 CH2 CH2 ONO OHC CH2 CH2 CH2 OH
Mec hanism:-

O N
H
O CH3 h O CH2 OH CH2 NO

NO

H N O N OH O
H
OH CH OH HC OH C
Proton
+ H2N OH
shift H+/H2O

4) AROMATIZATION
Alicyclic compounds which are reduction products of aromatic systems can be
dehydrogenated to the respective aromatics in several ways. The reagents used are:
(i) Sulphur or selenium (S or Se)
(ii) Palladium (Pd) on charcoal or asbestos
(iii) Quinones e.g. chloranil or DDQ
These methods are discussed hereby.

(i) Sulphur or Selenium (S or Se)

(a) Reaction occurs with sulphur at about 200 °C and with selenium at about 250 °C.
(b) The hydrogen being removed as hydrogen sulphide or hydrogen selenide.
(c) Skeletal rearrangements may occur and carbon atoms may also be removed.
(d) In particular, angular methyl groups and gem-dialkyl substituents are degraded, e.g.

24
 Dr. M. Athar Abbasi

H
H3C
C H3
Cholesterol C CH3
CH3 Chrysene
(5-Cholesten-3-ol) H C H3

CH3 H
1
H H S or Se
3 5 +
HO
H
Se is less destructive than S and is usually preferred but the methods are of more
value in degradation than in synthesis. Distillation with Zn dust has essentially the same
effect but is more destructive.

(ii) Palladium (Pd) on Charcoal or Asbestos

Alicyclic rings which contain some unsaturation can be dehydrogenated on those
catalysts which are successful for hydrogenation. Palladium on charcoal or osbestos is the
most commonly used reagent. The conditions are far milder than those using Se and the
procedure is widely applied e.g. the reduced isoquinolines obtained by the Bischler-
Napieralski synthesis are usually oxidized in this way.

Pd-C

H2
N N
(iii) Quinones
Partially unsaturated alicyclic rings are oxidized by quinones through hydride
transfer to the oxygen of quinone. The most commonly used quinones are chloranil or
dichlorodicyanobenzoquinone (DDQ). The former is cheaper one and the latter is more
powerful.
H H O H H
H
Cl Cl
H OH
+
Cl Cl Cl Cl
Chloranil
O +
OH Cl Cl
Cl Cl H H O
+
Cl Cl
OH
The driving force results from the conversion of both the O
quinone and the alicyclic system into aromatic compounds. Quinones NC Cl
which contain electron-releasing substituents are stabilized relative to DDQ
their quinols and are less powerful oxidants than those containing
NC Cl
electron-attracting substituents.
O
 REFERENCE BOOK:-
1. W. Carruthers, “Some Modern Methods of Organic Synthesis”, 3 rd edition,
Cambridge University Press, Cambridge.

25