Basic concept of Oxidation

¢ A Large number of reactions described in literature involve

oxidation. However a precise and comprehensive definition of
oxidationis difficult. A convenient definition for oxidation for
an organic compound is the addition or gain of oxygen or
removal of hydrogen.
* Thus, oxidation of an aldehyde to a carboxylic acid or
conversion of ethylene into ethylene oxide involves addition
of oxygen. On the other hand, oxidation of ethanol to
acetaldehyde involves removal of hydrogen.
 Remember this!!

* Leo, the Lion Says “GER”!!!

 Oxidation reactions in Nature

Rusting or iron
Cellular respiration
Photosynthesis
Bleaching action
Decomposition of dead organisms
Antiseptic action
Darkening of apple
Combustion
In the above example the reagent is reduced and so the
organic compound is oxidised. In a similar way in oxidation of
potassium permanganate Mn(VII) is converted to Mn (Il) or
Mn (IV).Oxidation in inorganic chemistry refers to los of one or
moreelectrons.
 Oxidation in inorganic chemistry refers to loss of one or moreelectrons.
4
Fe’ —— fe + € (oxidation)

* A most important definition of oxidation is that, an oxidation

reaction involves loss of electrons or increase in the oxidation
state. However, in Organic reactions, it is not easy to
determine weather a carbon atom loses or gains electrons.
But it is easy to calculate the changein oxidation state of the
carbon atoms and so classify a particular reaction as oxidation
or reduction.
Thus, the conversion of a functional group in a molecule, from
a lower oxidation state to a higher one will be termed as
oxidation., while the opposite of it would be reduction. It is
therefore, necessary to understand what the oxidation state
is.
 Oxidation state
* A comparison of oxidation statesof atoms in reactant and
product enable us to keep atrack of the transfer of electrons
in a chemical reaction. Oxidation state is equal to the change
an atom would haveif all the electrons in a covalent bond
wereassigned to the moreelectronegative atom. A number of
rules were forrgulated.

— The following convention for assigning oxidation number is

used. Oxidation number for hydrogen is -1; for carbon
(bonded to same atom) is 0; for carbon bonded to a hetero
atom is +1.
* The oxidation number of only those atoms are changed in the
reaction have to be examined. If the sum of the oxidation
numbersof various atoms in the substrate and in the product
is compared, the change in oxidation number can be
calculated and then we can find out whether the reaction is
an oxidation or reduction. Let us consider the conversion of n-
propanol to propanal.
 2€lost
CH;—CH,—CH,0H ——> CH;—CH,;—CHO
=] e +h

* In n-propanol, the carbon bearing the hydroxyl group has an

oxidation number of -1 (C is 0, H is -1 & O is +1). The oxidation
number of this carbon in propanal is +1 (C is 0, H is -1, 0 is +1
and O from the second bond to carbonyl is +1). We find that,
the changein oxidation number is -1 to +1, for a net loss of 2
electrons. So this is an oxidation reaction.
* The oxidizing power of the oxidizing reagent depends on their
oxidation potential. This represents the ability of a metal atom
to be ionized®to an ion (M in to M ions) with loss of an
electron. The oxidation of organic substrate is carried out by
transition metal compounds’ containing chromium,
manganese, ruthenium, selenium, silver or cerium.
The pH of the medium in which reaction is carried out also
plays an important role in the oxidizing power of a reagent.
The product obtained in an oxidation reaction depends on the
nature of the substrate, the reagent and the conditions
(Temperature, pressure, solvent etc)
 Manganese(VII) oxidants
* Potassium permanganate: Is a derivative heptavalent manganese
is a very powerful oxidizing agent. Its reactivity depends on
whether it is used in acid or neutral or basic conditions. In acid
solution, Mn (VII) is reduced to divalent manganese(II) with a net
transfer of five electrons (Mn VIII to Mn Il).
— However in neutral or basic medium, manganese dioxide is
usually formed, corresponding to a three electron change (Mn
VII to Mn IV). It is normally used in aqueous solution. Sinceall
compounds are not soluble in water, the use this compound is
limited. However, solvents which are not effected by this, such
as acetic acid, acetone, pyridine, t-butanol etc can also be
used.
* It is now well known that, the yields of potassium
permanganate oxidations are considerably improved by the
use of a phase transfer catalysts (PTC) and crown ethers. Even
the time required for the reaction is considerably shortened.
* Crown ethers are cyclic chemicalcompounds that consist of a
ring containing several ether groups. The most common
crown ethers are cyclic oligomers of ethylene oxide, the
repeating unit being ethyleneoxy,i.e., -CH,CH,O-. Important
membersofthis series are the tetramer (n = 4), the pentamer
(n = 5), and the hexamer(n = 6).
The term "crown" refers to the resemblance between the
structure of a crown ether bound to a cation, and a crown
sitting on a person's head. The first number in a crown ether's
name refers to the number of atoms in the cycle, and the
second number refers to the numberof those atoms that are
oxygen. Crown ethers are much broader than the oligomers of
ethylene oxide; an impottant group are derived from
catechol .
* Crown ethers strongly bind certain cations, forming complexes.
The oxygen atoms are well situated to coordinate with a cation
located at the interior of the ring, whereas the exterior of the
ring is hydrophobic. The resulting cations often form salts that
are soluble in nonpolar solvents, and for this reason crown
ethers are useful in PTCs.

* The denticity of the polyether influences the affinity of the

crown ether for various cations. For example, 18-crown-6 has
high affinity for potassium cation, 15-crown-5 for sodium
cation, and 12-crown-4 for lithium cation. The high affinity of
18-crown-6 for potassium ions contributes toits toxicity.
Crown ethers
 Oxidation by KMn0O4
* Oxidation of Alcohols : Oxidation of primary alcohols to
aldehydes is not normally carried out by potassium
permanganate, as the reaction proceeds to the carboxylic
acid. Primary and secondary alcohols are oxidized to
carboxylic acids and ketones respectively, containing the same
number of carbon atoms.
[O]
R—CH;CH,OH =———————»_ R—CH;COOH
MnO,4, H2SO. Z
1° Alcohol _ eae Carboxylic acid

2-methylpropan-1-ol is oxidized to 2-methylprpionic acid with

KMn0O4
R R
S
+ 3H,SO,——> 5 = + 2MnSO4
NcHOH + 2KMnO,
R’ R
2° Alcohol +K;$0, + 80
* Secondary alcohols however can be oxidized by KMn0O4 in
acidic or alkaline conditions to give the ketones

R.
see Z
ES /,C==O + 2MnSOs
5s CHOH + 2KMnO, + 3H;SO,——> 5
R R
2° Alcohol +K SO, + 8H,0

* The use of mild oxidizing agent like barrium permanganate

(which is quiet stable & easily availablef also oxidizes primary
& secondaryalcohols into carbonyl compounds.
Oxidation of alkenes : Alkenes on treatnent with dilute KmnO4 solution in
presenceofalkali give 1,2-diols. In this reaction, the purple KMnO4is reduced to
Mn0O2, a brownsolid. This change in the colour is the basis of test for the presence
of double and triple bonds knownas the Baeyer test for unsaturation.
The hydoxylation of alkenes with KMn0O4is carried out bystirring alkene and
the aqueous KMnO4 solution, eitMer neutral or slightly alkaline at room
temperature. Ex : Oleic acid in basic medium gives a glycol.

H OH
7 KMnO4 ae
Ca NaOH H™ \ 7H
CH;3(CH2)7 (CH2)7COOH cHyCHy! (CH2);COOH
Oleic acid
1,2-diol (ervthro)
KMnO, 9,10-Dihyroxystearic acid
(81%)
y neutral

Oo OH Qu g
CHA(CH2)7—C—CH(CH3)7COOH-— + CHy(CH);7CH—C—(CH);COOH
Hydroxyketones
Mechanism
* Oxidation of alkynes : Alkynes can be oxidized with KMnO4 to
give a mixture of carboxylic acids.
KMn0,
R—C=C—H + 4[(0] ——» RCOOH + co,
KMn0O,
R—C=c-—gR' + 4(0) ——*> RCOOH +. RICOOH

* Inthe above examples, Second reaction is used for the

structure elucidation of alkynes
Oxidation of aromatic side chain : benzene is an
exceptionally stable compound and is not effected by usual
oxidizing agents. For this reason bepzene is used as a solvent
in most of the organic reactions. If an alkyl group is present in
benzene nucleus, the side chain is oxidized to corresponding
carboxylic acid.

CH, OOH

:a (0) ee
e
Toluene Benzoic acid
alkaline KMnO, (40-50%)
8-10 hrs / reflux
cetyitrimethyiammonium (80%)
chloride / 4 hrs
 o-Chlorotoluene

ao ie
———e=-
4
CH, COOH
Mesitylene Mesitoic acid

KMn0,,
SN reflux : COOH
Quinoline Spe2,3-dicarboxylic acid
(Quinolinic acid)
COOH

ae Pyridine-3,4-dicarboxylic acid
wy (Cinchomeronic acid)
Oxidation of aldehydes & ketones: It can oxidize aldehydes &
ketones to corresponding carboxylic acids in alkaline medium
Jen
Be CHO + 2MnO, + OH ——+ 3 COO-

+2MnO, + 2H20
R R
yy | (p-Anisaldehyde) 4-CH; (p-Anisic aicd)
3,44OCH:)2 (Veratraldehyde) 3,4-(OCH3)2_ (Veratric acid)
Mechanism:
i
RR CHO 4: HOl 5, RCHOBE H20
* Oxidation of nitro compounds : Alkaline KMn0O4 oxidizes
primary and secondary nitro compounds into’ the
corresponding carbonyl compounds (aldehydes and ketones
respectively)
KMnO,4, OH
RCH2NO
~ = H20, 0-5°

NO2
| KMnOs, OH
2
H2O
* Manganese dioxide: This is a mild reagent & is useful for the
oxidation of primary & secondaryalcohols to carbonyl compounds.
This is specific for the oxidation ofallylic & benzylic alcohols. The
reaction takes place under mild conditions & neutral solvent. This
must be freshly prepared by the reaction of Manganese(II) sulfate
with KMn0O4in alkaline solution. MnO2 does not effect C-C double
bonds and triple bonds.
oC 3
CH;
I
CH==c: ‘CH: d CH0H MnO2 J Gy =—=C-——_CH==C—CH
CH3COCH3 5%)

_Mn02_
ether
‘CH2OH
eaeaee

_Mno2
cHcR
room temp.
ne
(Or)ONE e
 Chromium (VI) oxidants
One of the most versatile oxidizing agents is chromic acid, which is a
derivative of hexavalent chromium. It reacts with almost all types of
oxidizible groups. During oxidation, the hexavalent chromium (VI) is
reduced to chromium (Ill),the most stable oxidation state of chromium,
with a net transfer of 3 electrons ( Cr (VI) to Cr (III). Chromium (VI) oxide
(chromium trioxide) & potassium & sodium dichromate are the most
common reagents employed. CrO3 dissolves in water to form chromic
acid, which in fact a powerful oxidizing agent. Unlike KMnO4, which can
oxidize both in acid and alkaline or neutral medium, chromic acid is used
onlyin acidic solution.

CrO3 HO ———~ HOCr_OH

i
oO
Chromium trioxide Chromic acid
* Instead of chromium trioxide (which gives chromic acid on
treatment with water) a solution of sodium or potassium
dichromate in aqueous sulfuric acid can also be used; the
latter contains an equilibrium mixture of the acid chromate
(VI) ion and dichromate(VI) ion.
Cn07 + H,O === 2HCrO,4
Dichromate ion acid chromate ion
Chromium trioxide is also used in acetic anhydride, t-butanol
or pyridine. In these solutions the reactive species are
chromyl acetate , t-butylchromate or pyridine-
chromiumoxide, respectively.
[e) 9
Il Il
CHyCOOFO0CCH; (CHy;COFTOC(CHs |des =
0 oO
Chromy]acetate t-Butylchromate Pyridine-chromium oxide
Following are someof the chromium (VI) reagents which
have been used for different types of oxidations.
1. Chromium trioxide in water
2. Sodiune/potassium dichromate in Dil H2SO04
3. Chromium trioxide in acetic anhydride
4. Chromium trioxide in t-butanol
5. Chromium trioxide pyridine
6. Chromyl chloride in CCl4
7. Chromium trioxide in combination with sodium boratein
presence of PTC clay catalyst
8. Jones reagent-8N chromic acid solution in aqueous H2S04
9. Pyridine chlorochromate (PCC)
10. Chromium pillared clay catalyst
* Oxidation of alcohols : Primary alcohols on oxidation with
sodium or potassium dichromate in Dil H2S04 give the
corresponding aldehydes, which are oxidized further by the
same reagentto carboxylic acids.
2- 3 zz
3 RCH,OH + Cr,0,+4H,SO, ——> 3RCHO +7H,0+2Cr +4S0,
2- 3 =
3 RCHO + Cr,0, +4H,SO, ——= 3RCOOH+2Cr + 480, + 4H,0
* Also the aldehyde formed may react with the unchanged
alcohols under acidic conditions to form hemiacetal, which is
easily oxidized to an ester.
fo)
NajCr07 [0]
CH,(CH>),CH;OH ———_ CH3(CH»), CHO ——> CH3(CH3),COOH
HO,H)SO.
n-Butyl alcohol 7 (45%)
| CH3(CH2)xCH2OH
[0]
CH3CH»CH2COOCH2(CH2)2CH3 CH3(CH2)2,C HOHOCH>(CH3)2CH3
Ester [ , (Hemiacetal)
A hemiacetal or a hemiketal is a compound that results from the
addition of an alcohol to an aldehyde or a ketone, respectively.
The Greek word hémi, meaning half, refers to the fact that a
single alcohol has been added to the carbonyl group, in
contrast to acetals or ketals
o 4 OH
Jk + HO—R, — a MnoRe

Ri H 1H

Aldehyde Alcohol Hemiacetal

Ht OH
Oo
J + HO-R, — nnORg
Rj R', Ri Ry

Ketone Alcohol Hemiketal

* Secondary alcohols on oxidation with sodium /potassium
dichromatein dilute sulfuric acid gives ketones in high yields.
Ketones usually do not undergofurther oxidation.
3R,CHOH + Na,Cr,0, + 4H,SO, ———> 3R,CO + Na,SO, + Cr,(SO,), + 7 H,O

* In the above oxidation three moles of secondary alcohols

react with two moles ofCr (VI) to yield three moles of ketones
and two moles ofCr/(III)
R 0 z 0
N Il _slow all
SHOn +) HOOn SeAF 5 o-Ttron + HO
Rhee Ori:
Chromic acid cH
6
#20 .fast
R
Nc=o
Ye
R
 Jones reagent
* The oxidation of alcohols with chromium trioxide-agetate sulfuric acid
reagent is known as Jones reagent. This reagent is very selective as it is
useful for oxidation of alcohols which contain C-C doubleor triple bonds,
allylic or benzylic C-H bonds and other sensitive groups. Generally reaction
is carried out at 0-20 degreecelsius.
* Jones reagent oxidises primary alcohols to carboxylic acids
O]
HC: ‘C ‘CH *CHCH2OH to) = HC Cc ‘CH: CH: ‘COOH
Jones reagent i
60%)
* Howeverat zero degreecelsius, primary alcohols are oxidized to aldehydes

[0]
AAA, Jonesreagent KAKA _
oO
@)
85%

Secondary alcohols on oxidation with Jones reagentgive ketones.

°
ZOH [0] u
C,H,— C==C— CH’ ————— C,H,—C==c—c—cH,
cu, Jones reagent
 Chromium trioxide-pyridine complex

Chromium (VI) oxide-pyridine complex, CrO3.2C5HS5N is easily

obtained by the addition of chromium (VI) oxide to pyridine.
This reagent is known as Collin’s reagent and is useful for
oxidation of alcohols containing acid-sensitive functional
groups. °

Oxidations are generally carried out in DCM solution under

anhydrous conditions. The chromium trioxide pyridine
complex was used for the oxidation of primary & secondary
alcohols by Sarett.
 Pyridinium Chlorochromate (PCC)
* This reagent can be obtained by adding pyridine to a solution
of chromium (VI) oxide in hydrochloric acid.
\ N+ iL
Cro; + x N + HCI Y NH CrO3Ci

Pyridine @cc)

PCC is a mild, highly selective reagent and is used in organic

solvents such as CH2Cl2. PCC can oxidize primary and
secondaryalcohols to the corresponding carbonyl compounds

= ae PCC
yan
R!
R' = H (primary alcohol)
R' = alkyl (secondary alcohol)
* PCC is also useful for oxidizing an allylic carbon to keto group.
However in such case, the alcoholic group if present must be
protected before oxidation.
CsHi7z

mae
PCC, CH3 OO
atoms.
“A, N3
og
(55%)

* PCC also can be used for selective oxidation of alcohols

containing other acid sensitive groups such as double bonds.
e
 Chromium trioxide-pyridine complex

Chromium (VI) oxide-pyridine complex, CrO3.2CS5HSN is easily

obtained by the addition of chromium (VI) oxide to pyridine.
This reagent is known as Collin’s reagent and is useful for
oxidation of alcohols containing acid-sensitive functional
groups.

Go; + 2

Oxidations are generally carried out in DCM solution under

anhydrous conditions. The chromium trioxide pyridine
complex was used for the oxidation of primary & secondary
alcohols by Sarett.
 Oxidation with Peracids
Peracids in general are the compounds having the general
formula RCO3H, have been usedto effect the oxidation. Few
common peracids are : performic acid (HCO3H), peracetic acid
(CH3CO3H), Perbenzoic acid %C6H5CO3H), trifluoroperacetic
acid(CF3CO3H),m-chloroperbenzoic acid (m-CIC6H4CO3H) etc.
Performic & peracetic acids are generally prepared in situ by
the action of hydrogen peroxide on the corresponding
carboxylic acids.

RCOOH + H,0, == RCO3H + 4H,0

* Oxidation of alkenes : Peracids reacts with alkenes to give
stable three membered rings containing one oxygen atom,
epoxidesor oxiranes.
Mechanism : This reaction is believed to take place by the
transfer of oxygen atom from peracid to the alkene. The
reaction involves a one step process without intermediats.
Epoxidation is stereopespecific leading to the syn type
addition of oxygen atom.

\ 4 > NS
Ga) as c
JXeeae6%c—R —C— |
A >o + RCOOH
ea

Alkene Peracid Epoxide (Oxirane)

* The rate of epoxidation increased by the presenceof electron
withdrawing groupsin the peroxy acid; thus trifluoroperacetic
acid is more effective than peracetic acid. The rate of
epoxidation also increasesif the alkene has electron donating
substituents. Thus terminal alkenes reacts slowly with
peracids compared to alkyl substituted alkenes like butene-2.
R—CH=—=cCH, m-oCI
a C6aH4ayCOa4H.
bh re. UR Cu cr
(Terminal alkene) Sree =

=—, m-CCO
64 IC6H4C
3H O3H,
CH; dioxan, 0°
2-Butene

CH3 m-CiICgH4,CO3H
———__—_—
CHC
CH3
1,2-Dimethyl-1,4-cyclohexadiene - 1,2-Dimethyl-1,2-epoxy-
yclohexene
* The epoxidations with peroxy acids are stereoselective and
takes place by syn-addition to the double bond, which is
established by X-ray analysis of the products obtained. As the
cis alkene gives only cis epoxide and trans alkene gives only
trans epoxide, the reaction must be concerted i.e. the one
step mechanism retains the stereochemistry of the starting
alkenes.

Co6HsCO3H
SS

cis-Olefin stron

7 a C6HsCO3H RL 7
a

H R H \s/ ‘R
trans-Olefin sien Tiel
* The isolated alkenes are epoxidised before the conjugated
alkenes. This is believed to be due to diminisation of
reactivity of conjugated alkenes in epoxidation. This is
illustrated by the epoxidation of beta - myrcene.

a : m-CIC6H4CO3H
ii
su

&Myrcene
Oxidation of ketones : Ketones react with peracids like
perbenzoic acid or peracetic acid to give esters by insertion of
oxygen. This reaction is known as Baeyer-Villiger oxidation .
R 0
\. CoHsCOOOH il
/ =0 ——~ R—C—OR + CoHsCOOH
Ester

tl >
RL + C6Hs—C—O—O
Pn
R

O—O—OCCH:
Ve hat OR =
PE aa ee + CsHsCOO™ +
 O CF;CO3H

oO
A at
CF;CO3H O-C—CHs
CHC
* Oxidation of N-heterocycles : Heterocyclic compounds
containing nitrogen, Ex, pyridine and diazines on reaction with
peracid give rise to the corresponding N-oxides.

C) CH;CO3H OC)
>

SS SS +
N
|
Oo
Pyridine Pyridine N-oxide

Pyridazine
 S
|
N, Ay
o CoHsCO3H (7 CoHsCO3H
SX
N
Pyrazine ‘