Oxidation A
Oxidation A
Oxidation A
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
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
[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
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
3
Dr. M. Athar Abbasi
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
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
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
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)
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
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
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.
(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
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
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
H H O
CrO3 CO OH
+
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
13
Dr. M. Athar Abbasi
Diphenic acid
65%
O3 / solv ent
H2O COOH
COOH
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.
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
OH O
+
Fe3
+ H
H
O O O O O
F e3+
O O O O OH HO
HH
OH
FeCl 3
(excess) OH
Binaphthol
2H OH
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
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
Mechanism:
H H
NH 2 N NH
O
O H O O
O
Fe 3+ H+
H H2O
H
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.
+ +
17
Dr. M. Athar Abbasi
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 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.
C H3 COOH
Cl Cl
KMnO 4
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
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.
19
Dr. M. Athar Abbasi
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.
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
(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
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
23
Dr. M. Athar Abbasi
M e ch anism :-
CH 3 CH 3 CH 3
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.
(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.
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