1

The term oxidation can be defined in different ways:

Addition of oxygen to a molecule

Removal of hydrogen molecule from a given molecule

Loss of electrons
Addition of Oxygen i.e.
[O]
C C C C
An alkene
O
An epoxide or oxirane
Removal of Hydrogen from a Molecule
OH
-H
2
C C H
R
Removal of Electron or Loss of Electrons
CH C
O
R
O O
.
-e
Phenoxide anion
o
2
Phenoxide radical
2

Here a question arises how we calculate the oxidation of a carbon bonded with other atoms?
For calculating the oxidation state of carbon, we have to consider following two key things.
1 Carbon is often more electronegative (2.5) than some of the other atom which it bonds such as hydrogen has electronegativity 2.2. So in this case what we have to do?
2 Unlike metal-metal bond, carbon bonds are found all over the organic chemistry then how can we calculate the oxidation state.
There is a simple rule for knowing the oxidation states of an atom in a molecule or over all oxidation state of a reaction.
If the number of H atoms bonded to a C decreases, and/or if the number of bonds to more electronegative atoms increases, the Carbon in question will be oxidized (i.e. it will be in a higher oxidation state).
How we assign the oxidation state of carbon?
1.
Examine the groups attached to a carbon atom.
2.
Give the carbon a -1 oxidation number if the each atom attached to less electronegative atom than the carbon in question?
3.
Give the carbon a +1 oxidation number if to carbon is attached to more electronegative atom than the carbon in question?
4.
Give 0 to each other carbon atom attached to the particular carbon.
5.
Give 0 to undefined (R) group attached to particular carbon atom.
6.
= Double bond will stand for two single bonds
3

7.
≡ Triple bond will stand for three single bonds
8.
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 in any reaction weather oxidation state increased or decreased.
9.
Addition of a species containing XY to a double will not change the overall oxidation state of reaction (sum of the individual carbon states will be remain same). Such as: HBr, HOH, HNO
2
, HCl, etc
10.
Addition of a species Y-Y’ will definitely change the oxidation state of the reaction. Therefore, addition of Y-Y’ (eg. Br-Br) to a double bond is an
Oxidation, however, elimination of Y-Y’ from a single bond is reduction.
Now let us examine the molecules containing a single carbon
Overall oxidation number is -4
4

Why oxidation state is -4? Because carbon is attached with four hydrogen atoms which are less electronegative than carbon
Overall oxidation number is -2
Why it is -2? Because oxygen replaced one hydrogen atom and more electronegative than carbon.
Overall oxidation number is 0
Why oxidation state is 0? Because two oxygen replaced two hydrogen atoms and oxygen is more electronegative than carbon.
Overall oxidation number is +2
Why oxidation state is +2? It is due to the fact that three oxygen replaced three hydrogen atoms
5

Overall oxidation number is +4
Why oxidation state is +4? Because four oxygens replaced four hydrogen atoms
Overall oxidation number is +4
Why oxidation state is +4? Because four oxygen atoms replaced four hydrogen atoms
6

Oxidation number of C = 0
-1
H H
-1
H C C
-1
H
C
-1
O
C
+1
+1
H
-1 H
2
O
-1 H
6 X (-1) = -6
2 X (+1) = +2
TOTAL = -4
-1
H
+1
Br C
-1 -1
H H
C C H
-1
-1
H
+1
O
+1
-H
2
O
H
2
O
-1
H
-1
H
C
+1 -1 +1
OH H O +1
C C C H
-1
-1 H
-1
H H
-1
7 X (-1) = -7
3 X (+1) = +3
TOTAL = -4
+1
Br
-1
H
C
H
-1
C
+1
OH
C
H
-1
H
-1
-1
H +1 OH
5 X (-1) = -5
3 X (+1) = +3
TOTAL = -2
5 X (-1) = -5
3 X (+1) = +3
TOTAL = -2
7

-1
H
-1
H H
-1
H
-1
-1
H
-1
H C
+1
S
+1
C C C C C
+1 +1 +1
N
-1 H H
-1
H
-1
9 X -1 = -9
5 X +1 = +5
TOTAL = -4
OXIDATION STATE:
-4
-3
-2
-1
0
+1
+2
+3
+4
Molecules
CH
4
RCH
3
CH
3
-OH, R
2
CH
2
RCH
2
OH
CH
2
O, R
2
CHOH
RCHO, R
3
COH
HCO
2
H, R
2
CO
RCOOH
CO
2
, CO
4
Generally no oxidation state change in the total organic molecule is observed in reaction like Hydrolysis or comparable reactions with alcohols (alcoholysis) or amines
(aminolysis) with addition or elimination of HX , HOH , and HOR or with tautomerization but oxidation occurs when oxygen added to the molecule.
8

9

10

Oxidation of alkenes may take place at the double bond or at the adjacent allylic position.
X
H
Alkynes
H OH
Halohydrins, Amino hydroxy
O O
Dioxetanes
HO H H
OH
Anti or Trans diol
H H HO
Cis diol
OH
Cleavage of Doble Bond
Carbonyl and Caboxylic Acid
H H
H O
Epoxide
H
11

Some oxidation reactions of alkenes give cyclic ethers in which both carbons of a double bond become bonded to the same oxygen atom. These products are called epoxides or oxiranes. An important method for preparing epoxides is by reaction with peracids, RCO
3
H. The oxygen-oxygen bond of such peroxide derivatives is not only weak (35 kcal/mole), but in this case is polarized so that the acyloxy group is negative and the hydroxyl group is positive.
Epoxides or oxiranes are the important intermediates in synthetic organic chemistry. The facile epoxide ring opening is extensive useful in C-C bond formations and diol preparation etc.
Epoxidation of alkenes are usually carried out by using peroxy acids.
1.
Peracid Reactivity
Reactivity Increases
R CH
3
C
6
H
5
m-ClC
6
H
5
p-NO
2
C
6
H
5
o-CO
2
C
6
H
5-
CF
3
3.4 2.9 0 pKa 4.8 4.2 3.9
The lower the pKa, greater the reactivity.
12

13

The reaction involves the nucleophilic attack on the O-O bond by the
-electron of the double bond.
Therefore
Epoxidation takes place more rapidly and preferentially at electron rich double bonds.
The reaction-rate increase when the substituents on alkenes are electron releasing.
This is the basis of regioselectivity in epoxidation.
Tetra subs. > Tri subs. > Di subs. > Mono subs. > Unsubs.
Similarly, electron withdrawing groups on alkenes decreases the rate of reaction.
O
F
Cis-alkenes give Cis Epoxides
Trans-alkenes give Trans Epoxides
Concerted reaction at one of the double bonds through cyclic intermediate is the basis of stereocontrol.
When two faces of the
-bond are unequally shielded, the two expected stereoisomers will not form to the same extent.
14

The reaction has relatively low steric requirements and even hindered alkenes can be epoxidized easily.
Stereochemistry of olefins is maintained: Diasterespecific
Reaction rate is insensitive to solvent polarity implying concerted mechanism without intermediacy of ionic intermediate
Less hindered face of olefin is epoxide
If,
R = H 20 min, 25
°
C
24 h, 25
°
C
99% 1%
R = CH
3
< 10% 90%
Epoxidation of an alkene containing one or more chiral centers gives two diastereomeric epoxides, depending on the face from which the reagent approaches the
-bond. This chiral induction is cause of diastereoselectivity in epoxidation.
15

Electron-withdrawing groups on peroxy acids increase the reaction rate.
is most commonly used reagent in epoxidation.
It is fairly stable, solid, and soluble in many organic solvents, such as CH
2
Cl
2
,
CHCl
3
.
Caution: It is SHOCK SENSATIVE
Subsequent work-up depend upon the stability of resulting epoxide.
Mechanism:
When epoxide react with water in the presence of catalytic amount of acid or base ring opening takes place to afford vicinal diol and it is a well known fact that the epoxide ring opening always takes place in trans manner so we will get an anti diol product in the result of epoxide ring opening e.g.
16

H
3
C
H
C
H
1) m-CPBA
C
CH
3
2) H, H
2
O
Trans 2-butene
HO
H
3
C
H
C
H
C
OH
CH
3
meso 2,3-butane diol
H
H
3
C
C
H
1) m-CPBA
C
CH
3
2) H, H
2
O
HO
H
H
3
C
C
H
C
OH
CH
3
+ H
3
C
H
HO
C C
OH
H
CH
3
Cis 2-butene
(2R,3R)-2,3 butane diol (2S,3S)-2,3 butane diol
The reactivity of alkene depends on the degree of substitution.
1. Monosubstituted terminal alkenes are least reactive.
17

Substituted versus Terminal Alkene
2. Deactivated double bonds are less reactive.
Deactivated Deactivated
O
C
OCH
3
MCPBA, CH
2
Cl
2
20 o
C
O
F
C
OCH
3
O
F
70%
3. The oxygen transfer is stereospecifically syn the stereochemistry of the starting alkenes is retained in the product. e.g.
D
C C
H
m-CPBA
H D
Trans alkene
H H
m-CPBA
C C
D C
O
C H
H
H D
Trans Oxirane
C
O
C H
D D
Cis alkene
D D
Cis Oxirane
4. Conjugation of alkene double bond with other unsaturated groups such as CN,
NO
2
, COR, COOR, SO
2
etc reduce the rate of epoxidation because of the delocalization of
electrons.
O
OH
CH
3
COOOH
18

It requires strong reagents e.g. MCPBA, triflouro per acetic acid at higher temperature
5. If one or more chiral centers present in substrate the epoxidation will be diastereoselective.
SiMe
2
Ph
MCPBA, CH
2
Cl
2
, 20 o
C
SiMe
2
Ph
O
+
SiMe
2
Ph
O
Anti face
67%
Peroxy attack takes place majorly from the anti face to the bulky silyl group.
33%
6. In general, for linear chain and flexible cyclic molecule, it is very difficult to predict the stereochemical out come of the reaction.
RO
MCPBA, CH
2
Cl
2
, 20 o
C
OAc
RO
O
47%
+
RO
OAc
O
53%
OAc
19

6. With conformationally rigid cyclic alkenes the epoxidation generally takes place from the less hindered side of the double bond in stereoselective fashion.
Less hindered face
MCPBA, CH
2
Cl
2
, 20 o
C
H
H
More hindered face
H
94%
O
H
+
6%
H
H
O
20

H
H
Equatorial
H
H
3
C
Less hindered
H
3
C
H
3
C
H
3
C
H
H
O
87%
H
CH
3
H
+
H
3
C
H
More hindered
CH
3
H
O
Axial methyl
H
13%
CH
3
Less hindered
H
3
C
CH
3
CH
3
H
3
C
CH
3
CH
3
Pseudoaxial
CH
3
O
More hindered
CH
3
O
CH
3
Axial methyl
MCPBA, CH
2
Cl
2
24 h, r.t.
H
3
C
H
3
C
CH
3
+
CH
3
H
3
C
H
3
C
CH
3
CH
3
93%
7%
21

7. Folded molecules are epoxidized selectively from the less hindered side.
More hindered
O
O
O
O MCPBA, 3 h, 5 o
C
O
O
O
95%
O
Less hindered
H
H
O
OBn MCPBA, 3 h, 5 o
C
OBn
H H
OBn H H
OBn
PhSiO
PhSiO 72%
8. Unhindered exomethylenic cyclohexene undergo preferential axial epoxidation
More hindered
CH
3
Ph
CH
2
MCPBA
CH
3
Ph
O
Ph CH
3
Less hindered
86%
22

9. Stereoselectivity is even more pronounced in polar solvents, since in polar solvents the effective steric bulk of the peroxy acid in the transition state become somewhat greater make attack from hindered side even more difficult.
H
3
C
H
3
C
CH
3
H
More hindered
CH
2
C
11
H
23
COOOH
Less hindered
H
3
C
H
3
C
CH
3
H
O
+ H
3
C
H
3
C
CH
3
H
(C
2
H
5
)O
CH
2
Cl
2
65%
83%
35%
17%
O
10. The polar substituent at allylic and homoallylic positions influence the direction of the attack.
OH
OH
Cis to OH
C
6
H
5
COOOH, C
6
H
6
, 0 o
C
O
Association of reactant with hydroxyl group of the substrate through hydrogen bonding cause preferential attack from that side.
In contrast if no hydrogen bonding occurs than it attacks from less hindered side.
23

OH OCOCH
3
C
6
H
5
COOOH, C
6
H
6
, 0 o
C
OCOCH
3
O
Normal Product
No hydrogen bonding i.e. attack from less hindered side
Mechanism of directive effect:
H O
H
CMe
3
C
6
H
5
COOOH
C
6
H
6 O
H
H
H
CMe
3 H
H
CMe
3
O
O
C
6
H
5
C O
H
CMe
3
HO
H
H
O
O
O
R
H
96%
O
H
+
HO
H
H
4%
O
H
H
O
O +
C
O
R
24

The effect is also observed in open chain compounds.
CH
3
C
6
H
5
H
2
CO
CH
2
OH MCPBA
CH
2
Cl
2
, 0 o
C
C
6
H
5
H
2
CO
CH
3
Coordination of MCPBA with ethereal and hydroxyl oxygen direct the attack from that side.
11. In acyclic alkenes the directive effect of polar allylic substituents is based on the
R
1
R
2 stability of transition state.
HO
R
3
MCPBA
CH
2
Cl
2
, 0 o
C
R
1
R
2
O
HO
R
3
+
R
1
R
2
O
HO
R
3
Threo Erythro
CH
2
OH
O
OH
H
R
3
H
R
2
R
1
H
H R
3
R
2
R
1
OH
Rotamer for threo
Rotamer for Erythro
Less stable due R
1
, R
3
interaction
When R
1
and R
2
are alkyl more threo will be stable
Trisubstituted or Cis - disubstituted Threo
Trans - disubstituted or monosubstituted
Erythro
12. In cyclohexene system pseudoequatorial hydroxyl is more effective than the pseudoaxial hydroxyl in directing epoxidation.
25

Homoallylic group can also direct the attack. Homoallylic axial hydroxyl can direct the attack, but homoallylic equatorial cannot.
Pseudo equatorial (Effective)
O
OH
OH
MCPBA, THF, 48 h r. t.
N
N
OH
OH
Homoallylic equatorial and cannot direct
69%
Pseudo axial (not effective)
Homoallylic axial (Effective)
OH
OH
HO
HO
O
MCPBA
HO
OAc
CO
2
CH
3
MCPBA, CH
2
Cl
2
0 o
C, 1 h
HO
O
91%
75%
OAc
CO
2
CH
3
26

CH
3
CH
OH
3
Ph
OH
CH
3
OH
MCPBA, CHCl
3
0 o
C, 1 h Ph
O
97%
Trans
Directive effect of hydroxyl is not large enough to overcome the steric interference
Ph
Less hindered
13. Besides hydroxyl, carbamates, ethers and ketones also direct the epoxidation.
O O
O N
CH
3
CH
3
O N
CH
3
CH
3
MCPBA, CH
2
Cl
2
, 0 o
C
O
97%
Hydrogen bonding between MCPBA and the carbonyl is the basic reaction of directive effect.
27

OSiBuMe
2
OSiBuMe
2
OSiBuMe
2
CF
3
COOOH, CH
2
Cl
2
, -40 o
C
O +
Bu Bu Bu
93%
7%
Directive effect is due to hydrogen bonding between hydroxyl of peroxy and allylic ether.
Electrolysis and microorganism such as Corynebactrium equii have also been used for epoxidation.
H
H
H H
H O O
+
C O
+
R
C
Alkene
H
R O H
Per oxy carboxylic acid
H O
Epoxide
H
O
H
O
O
O
H O
R
O + RCOOH
Epoxide or Oxirane

Per acids are not only way for epoxidations

t-BuOOH with V +5 or Mo +6 species are also used for epoxidation.
28


t-BuOOH with Mo +6 species are excellent for epoxidation of isolated double bonds.

t-BuOOH with V +5 species are excellent for epoxidation of allylic alcohol and
Terminal alkenes.
t-BuOOH
V
+5
O
Terminal alkene Difficult to epoxidize with peroxyacid
V(acac)
2
OH t-BuOOH
O
OH
+ OH
93%
O
7%
m-MCPBA O
OH
+
65%

Controls the stereochemistry of resulting epoxide.

Allylic

Homollylic

Bishomoallylic
 or even remote position
O
35%
OH
29

OH
OH
O
V(acac)
2
t-BuOOH
83%
OH
Mo(Co)
6
t-BuOOH
O

Precise cause of reaction in not very clear

Very fast
 High stereoselectivity

Formation of intermediates

Minimum steric interactions
R
1
R
2
O
L
V
R
3
L
O
O
OH
t-Bu
R
4
30


Epoxidation of allylic alcohol







t-BuOOH
Ti(iPrO)
4
Natural L-(+)-diethyl Tartarate
Unnatural D-(-)-diethyl Tartarate
High optical purity
Diseterofacial stereoselectivity
Sharpless epoxidation
L(+)-Diethyl Tartarate
Ti (iPrO),t-BuOOH
R
OH
Prochiral allylic alcohol
D(-)-Diethyl Tartarate
Ti (iPrO),t-BuOOH
The discovery of epoxidation.
K. B. Sharpless, Chem. Brit. 38. 1986 and references therein.
O
R
OH
90%
O
R
OH
90%
31

High asymmetric induction
Absolute configuration of product is predictable
(+) or (-)- Tartarate ensure one or other epoxide in over 90% optical purity.
D(-)-Diethyl tartarate
(Unnatural)
:O:
R
2
R
3
TOP :O: Delivery
R
1
R
2
Ti(iPrO)
4
, t-BuOOH
OH
CH
2
Cl
2
, -20 o
C
R
3
R
1
O
OH
:O:
L(+)-Diethyl tartarate BOTTOM :O: Delivery
(Natural)
Top or Bottom [O] delivery depends on the isomers of tartarate used and depends on pre-existing chirality of substrate. In a recemic Titanium complex reacts with only one enantiomer.
32

D(-)-Diethyl tartarate
:O:
(Unnatural)
Ti(iPrO)
4
, t-BuOOH
O
Slow Top attack due to bulky R group
OH
OH
R
:O:
L(+)-Diethyl tartarate
(Natural)
Ti(iPrO)
4
,t-BuOOH
R
O
OH
Fast bottom attack due to bulky R group
R
H
D(-)-Diethyl tartarate
(Unnatural)
:O:
Ti(iPrO)
4
, t-BuOOH
H
O
OH
Fast top attack due to bulky R group
R
OH
:O:
R
L(+)-Diethyl tartarate
(Natural)
Ti(iPrO)
4
, t-BuOOH
O
OH
Slow bottom attack due to bulky R group
R
Diseterefacial stereo selectivity
K. B. Sharpless, J. Am. Chem . Soc, 1981, 103 , 6237.
33

Ti(OR)
4
+ Diethyl tatarate
[Ti(DET) (OR)
2
] + 2ROH
TBHP
ROH
[Ti (OR) (TBHP) (DET)]
ROH Allylic alcohol ROH Allylic alcohol
[Ti (OR) (Allylic alcohol) (DET)]
TBHP
ROH
[Ti (TBHP) (Allylic alcohol) (DET)]
[Ti (OR) (epoxy alcohol) (tatarate)]

Rapid ligand exchange of Ti(O-i-Pr)
4
with DET.

The resulting complex further ligand exchange with the alcohol and then
THP.

The exact structure of the active catalyst is difficult to determine due to rapid exchange but it is likely to have dimeric structure.

The hydroperoxide and the allylic alcohol accopy the axial coordination sit on the titanium and this account for the enantionfacial selectivity.
 Oxygen transfer from TBHP to allylic alcohol to give a complex [Ti(OBu)
(epoxy alcohol) (Tatarate)] This is a slow step.
 Both Ti(OR)
4
and Ti(Tartarate) (OR)
2
are active epoxidizing catalyst. Ti
(Tartarate)
2
is catalytically inactive

Excess of Ti(OR)
4
and its contribution in epoxidation will results in loss of enantioselectivity because it is achiral.

Excess of Ti(Tartarate)
2
causes a decrease in reaction rate.
34

 10-20% mol% excess of tartarates over titanium results in the formation of
Ti (tatarate) (OR)
2 which gives high enantioselectivity and acceptable rate of reaction.

Since the reactions involve a nucleophilic attack on peroxy oxygen in the reactions the electron rich alkene reacts faster than electron deficient alkenes. For example in case of substituted cinnamyl alcohols, an electron-withdrawing (p-nitro) group decreases the reaction rate while electron donating (p-methoxy) increase the rate of reactions.
H OH H OH
NO
2
OMe
Slow reacting p-nitro cinnamyl alcohol Fast reacting p-methoxy cinnamyl alcohol
Highly subtituted double bond epoxidize prefereably than less substituted
OH
(CH
2
)
10
Highly substituted double bond
O
OH
(CH
2
)
10
35

36

E O
Ti
O
(2)
O
(1)
E
A reaction path way invoking orbital controlled approach of C-C bond to the peroxide oxygen O(1) in the direction of axis of O(1)-O(2) in the complex has been suggested by Sharpless
K. B. Sharpless et. al. Pure and Appl.Chem., (1983) 55, 589.
37





Homoallylic alcohol
Transfer of stereochemistry by phosphate and
Cyclic iodophosphate formation
Treatment of cyclic iodophosphate with ethoxide
OH
OP(OR)
3,
I
2
,
CH
3
CN, NaOEt, 25 o
C
OH O
Mechanism:
OH
RO
O
P
OR
OR
O
O P
RO
OR
I I
I
RO P
R
O
O
O
O
P
O
O
OR
OR
OR
I
-RI
O O
P
O
OR
I
OR
OH O
+
O
P
RO
RO
OR
38

Oxidative cyclization or Iodolactonization
O
HO
O
Mechanism:
I
2
, CH
3
CN, 0 o
C HO
O
HO
O
OH
I I
O I
O
O I
+
O
O I
Na
2
CO
3
CH
3
OH, 25 o
C
H
3
CO
O
Iodolactone (10:1)
What will be the mechanism of last step?
O
39

It is very useful method for epoxidation of terminal double bond.
OH
B
Mechanism:
NBS, H
2
O
DME Br
O
O
Br N
O
+ H
2
O
OH
Br
B
OH
2
Br
O
40

H
3
C
CH
3
CH
3
NaOMe
MeOH
H
Mechanism:
H
3
C
O
H
3
C
H
3
C
Y
O
H
CH
3
H
3
C
Y
O
H
CH
3
Transition state
H
3
C
H
O
CH
3
CH
3
H
2
SO
4
MeOH
H
3
C
H
3
C
CH
3
H
3
C
Y
H
O
CH
3
Alkoxide Ion
H
C
OH
OCH
3
CH
3
C C CH
3
H
OCH
3
C CH
3
CH
3
OH
CH
3
H
3
C
Y
H
OH
CH
3

-Substituted alcohol
Mechanism:
H
3
C
H
O
CH
3
CH
3
H
H
O
Me
Fast
Slow
H
3
C
HO
CH
3
H
3
C
O
H
CH
3
MeOH
Fast
H
3
C
H
CH
3
CH
3
H
O
Me
O
H
H
3
C
HO
H
3
C
O
CH
3
CH
3
41

4
An aqoues solution of KMnO
4
reacts with olefins to add hydroxy function to double bond in a cis manner provided the reaction mixture is alkaline. If the reaction mixture is kept neutrals either by continuous addition of acid or by adding magnesium sulfate the permagnate oxidation results in cleavage or in the formation of α-hydroxy ketone.
H
HO
2
C(H
2
C)
7
C
H
C
(CH
2
)
7
CO
2
H
KMnO
4
NaOH (excess)
H
2
O
HO OH
H
HO
2
C(H
2
C)
7
C C H
(CH
2
)
7
CO
2
H
81%
KMnO
4
, H
2
O
CH
3
(CH
2
)
7
C (CH
2
)
7
CO
2
H
O
75%
KMnO
H
2
4
NaOH
O, t-BuOH, O
o
C
KMnO
4
MnSO
4
H
2
O, AcOH, -15 O o
OH
HO
40%
CHO
H
H
54-66%
CHO
42

4
There are two ways
Gives vicinal diols
R
R
OH
CH HC
KMnO
4
CH
R
(Olefin)
HC
OH
R
(Cis diol)
4
43

4

Cis vicinal diol

Mechanism is very simple

Expensive and highly toxic reagent

Better yield than KMnO
4

Strained and unhindered olefins react rapidly

Catalytic amount of OsO
4 with less expensive oxidant works well.
CH
3 CH
3
OH
OsO
4
OH
CH
3
CH
3
70%
R
CH
O
Os
CH
O
O
O
R
R
H
C
C
H
R
OsO
4
H
2
O
2
R
H
C OH
C OH
+ OsO
4
H
R
R
HC
HC
R
O
O
O
Os
O
H
2
O
R
HC
HC
R
OOsO
2
OH
R
HC
HC
R
OH
OH
44

Prévost’s Reagent (I
2
/CCl
4
+AgOAc) or (I
2
/CCl
4
+AgOBz)
AcO OH
H H
+
H 2
O
I
2
/CCl
4 anhy
con drou ditio n s
OAc
H H
AcO
Reaction of alkene with Prévost’s reagent in a solution of iodine in CCl
4 together with one aqueous solution of silver acetate or silver benzoate under anhydrous condition (Prévost’s conditions) the oxidant directly yields the diacetyl derivative of the trans-glycol. While in the presence of water the monoester of the cis-glycol is obtained (Wood wards conditions)
The value of this reagent is due to its specificity and to the mildness of the reaction conditions, free iodine, under these conditions used, hardly affects other sensitive groups present in the molecule.
Reaction proceeds through the formation of iodonium ion.
45

Mechanism:
I I
CH
3
AgO
O
C
CH
3
O O
Ag
O O
O
C C
I
Iodonium Ion
CH
3
O
C CH
3
+ AgI
I
OH OCOCH
3
H
2
O
H
3
C
O
OH
O
CH
3
O O
OCOCH
3
OCOCH
3
H
C C
H
OCOCH
3
Diacetyl Trans diol
Prevost Method Monoacetyl Cis diol
Wood wards Method
46

The most general and mildest method of oxdatively cleavage of alkene to carbonyl compounds is Ozonolysis
Alkene is treated with Ozone (O
3
) at low temperature in solvents like methanol, ethyl acetate and dichloromethane.
The first insoluble intermediate ozonide forms which is reduced to the two carbonyl products by different treatment like cat. hydrogenation, Zn/HOAc or by reaction with dimethyl sulfide.
O
H
3
C
C
2
H
5
3
O O
O
Ozonide
Reduction
H
O
3,
CH
2
Cl
2
CH
3
Zn/HOAc
CH
3 O
3,
CH
2
Cl
2
Zn/HOAc
O
+
O
O
+
O
O
H
CH
3
H
CH
3 CH
2
O
3,
CH
3
OH
(CH
3
)
2
S
CH
3 O O
+
H H
O
47

STEP 1:
O
O
O
O O
O
Molozonide
O
+
O
O
STEP 2:
O
(CH
3
)
2
S
+
(CH
3
)
2
S=O
O
O
O
Zn/HOAc
C C
+
ZnO
O
O
O O
O
H
2
/Pt
Ozonoide +
H
2
O
Treatment of the ozonoide with NaBH
4
leads to alcohols. In this way, a double bond can be oxidatively cleaved to produce two alcohols.
CH
3
(CH
2
)
2
CH CHCH
2
CH
2
CH
3
1. O
3
, CH
2
Cl
2 2CH
3
CH
2
CH
2
CH
2
OH
2. NaBH
4
,/CH
3
OH
O
C
O
OCH
3
1. O
3
, CH
2
Cl
2
2. NaBH
4
,/CH
3
OH
C
2
H
5
OH + HOCH
2
(CH
2
) C CH
3
CH= CH
3
(CH
2
)
7
OCH
3
48


Iradiation of alkenes and conjugated dienes in the presence of oxygen

Hydroperiodes Reduced to alcohol

Alkene to allylic alcohols

Sensitized Organic dyes (fluorescence derivatives, methyl blue, propylene derivatives

No reaction if lack of allylic hydrogen

= = = = = = = = = sensitizer

= = = = = = = = = O
2

= = = = = = = = = light
H
H OOH
C
H
C C
O
2
Sensitizer
C
H
C C H
Reduction an allylic hydrogen
H H
The position of double bond changes from α, β to β, γ.
C
H
C C
OH
H
H
49

Generally proceed by a concerted mechanism
C
C
H
H
3
O
C
O
H
3
C
O
O
CH
3
C
C
H
C
O
O
Red an allylic hydro peroxide
H
3
C CH
3
C C CH
2
OH
An allylic alcohol
CH
3
H
3
C
O O
CH
2
H
H
3
C CH
3
H
3
C
O
O
CH
2
H
H
3
C CH
3
H
3
C
OOH
CH
2
50

2

SeO
2
is a useful reagent for allylic oxidation of alkenes.
 Products include allylic alcohols, allylic esters, enals depending upon the nature of substrate and reaction conditions.
R H
R H
H CHO
H CH
3 H H
R CH
2
OH
Basic mechanism consists of three steps: i) An eletrophilic ene reaction with SeO
2
Ene reaction: Certain electrophilic double bonds undergo an addition reaction with alkenes in which an allylic hydrogen is transferred to electrophile.
R
O
Se
O
R
O
Se
O
R
O
Se
H
H
O
H
H
H H
Allylic Selenic Acid
51

ii) A sigmatrpic rearrangement that restore the original location of double bond because in the first step the position of double bond has been disposed.
OH
OH
R
Se
O
R
Se R
OH
O Se
O
H
H
Finally hydrolytic breakdown of resulting selenium ether
R
OH
R
Se H
2
O/H
+
H
H
O
H
OH
Normally an excess amount of this reagent is used due to which resulting alcohols are further oxidized to aldehydes ,
R R
SeO
2
OH
O
H H
Therefore, a modification is carried out in order to avoid further oxidation. i) Reaction was carried out in acetic acid as solvent
OH
R R
Se AcOH + Se(OH)
2
O OAc
H H
Allylic acetate ester can be hydrolyzed to required allylic alcohol. ii) Use of catalytic SeO2 along with co-oxidant t-BuOOH which regenerate the catalyst repeatedly and product will be allylic alcohol.
52

i) In trisubstituted alkenes, oxidation occurs at more substituted end of the double bond.
H
3
C CH
2
CH
3
H
3
C H
Oxidizable site ii) The oxidized product will be E-allylic alcohol
H
3
C CH
2
CH
3
HOH
2
C H
The observed stereochemistry can be explained by considering the five membered cyclic transition state for sigmatropic rearrangement.
OH
H
C
2
H
5
Se
HO
O
C
2
H
5
H
3
C
O Se
H
3
C HOH
2
C
C
2
H
5
CH
3
Transition state for E-allylic alcohol
HO
H HOH
2
C C
2
H
5
O Se
H
3
C H
CH
3
Transition state for Z-allylic alcohol
C
2
H
5
H
53

Salient Features:
1.
Offers a direct conversion of alkenes to carbonyl compounds.
2.
Atmospheric O
2
is used in presence of PdCl
2
and CuCl
2
as catalysts known as
Wacker-Smidt process. PdCl
2
is used in catalytic amounts while CuCl
2
is stoichiometric co-oxidant.
3.
Oxidation reaction is carried out in water in the presence of HCl.
4.
Terminal alkenes react at much faster rate than internal or 1,1-disubstituted alkenes.
5.
α,β-unsaturated ketones and esters are oxidized regioselectively to corresponding β-keto compounds using catalytic amounts of Na
2
PdCl
4
and
H
2
O
2
as co-oxidant.
The catalytic cycle can also be described as follows:
[PdCl
4
]
2 −
+ C
2
H
4
+ H
2
O → CH
3
CHO + Pd + 2 HCl + 2 Cl
−
Pd + 2 CuCl
2
+ 2 Cl
−
→ [PdCl
4
]
2−
+ 2 CuCl
2 CuCl + ½ O
2
+ 2 HCl → 2 CuCl
2
+ H
2
O
Wacker Oxidation
54

55


Several methods
→ Chemical → Catalytic → Microbial etc → Produces →, Aldehydes → Ketone
→ Acids
 Primary alcohols → Aldehydes or carboxylic acid
 Secondary alcohols → Ketones
 Tertiary alcohols → Cleavage of C-C bond
Primary Alcohols ……………………. Aldehydes, Carboxylic Acids
Secondary Alcohols …………………... Ketones
Tertiary Alcohols ……………………….. Cleavage of C-C bond
Alcohol Oxidation must focus

The relative strength of the reagent

The condition under which is used

Structure variation of the alcohols
Oxidizing properties of Chromium with respect to media

Chromium (VI) in acidic media

Chromium (VI) with heterocyclic nitrogen bases
56

O
HO Cr O
-
O
-
O Cr
O
O Cr O
-
+ H
2
O
O
J. Am. Chem. Soc., 1958, 80, 2072
J. Am. Chem. Soc., 1960, 82, 290
O O
CH
3
O CH
3
O
H C OH HO Cr OH
H
+
-H
2
O
H C O Cr OH
CH
3
O CH
3
O
Chromate ester
O
HO
Cr
OH
+
Cr(VI)
J. Am. Chem. Soc., 1959, 81, 2116
H
3
C
O
Cr(IV)
CH
3
57

In cyclohexanol axial OH generally oxidized rapidly than equatorial
O
OH O Cr OH
O
Axial Less stable due to 1,3-diaxial interaction
OH
O
O Cr OH
O

Conformation can be determined
 Primary → aldehyde → carboxylic acid

Continuous distillation of aldehyde

Not suitable for alcohols containing acid sensitive group

Different solvent combinations

Na
2
Cr
2
O
7
/H
2
O
4
/H
2
O

CrO
3
/HOAc/H
2
O

CrO
3
/H
2
SO
4
/H
2
O/Acetone (Jones Reagent)

CrO
3
/H
2
O/HCl/Oxalic acid

CrO
3
/DMF

CrO
3
/HMPA
CrO
3
/DMSO/H
2
SO
4
Aqoues / Non aqoues, Heterogeneous, Phase Transfer and Solid Support conditions can also be used.
58

Most widely used method of oxidation using
Chromic acid/sulfuric acid in aqueous acetone
Protect the substrate from over oxidation
Multiple bonds are not attacked by Jones reagent
OH
J. R.
O
H
3
C
NHTs
CH
3
H
3
C
98%
CH
3
NHTs
O
OH
J. R.
CH
3
Bu
OH
1.
J. Org. Chem., 1976, 41, 177.
2.
J. Org. Chem., 1971, 36, 387.
3.
Can. J. Chem., 1976, 54, 3113.
J. R.
CH
3
84%
Bu
82%
O
O
59

i) Chromium (VI) oxide forms complex with several nitrogen heterocyclic compounds which show oxidizing properties. ii) They are milder more selective oxidants than acid based reagent systems. iii) Acid sensitive group are tolerated. iv) Preparation of aldehyde is generally easier.
a)
Chromium trioxide pyridine complex (Sartt’s reagent)
O
N
+
Cr O
-
O b) Dipyridine chromium (VI) oxide (Collin’s Reagent)
O
-
O
-
Cr
N
N
O c) Pyridiium Chlorochromate (Corey’ Reagent) d) Pyridinium dichromate
N
+
H
ClCrO
2
N
+
H
Cr
2
O
7
-
3
-
60

O O
OH
PCC
3 eq. CH
2
Cl
2
, 1 h, r.t.
O O
O
H
Can. J. Chem., 1987, 65, 195.
MeO
OMe
PCC
H
OH 1.4 eq. CH
2
Cl
2
, 2 h, r.t.
NaOAc
MeO
J. Am. Chem. Soc., 1980, 102, 1983
OMe
O
a)
Chromium trioxide pyridine complex (Sartt’s reagent)
O
N
+
Cr O
-
O b) Dipyridine chromium (VI) oxide (Collin’s Reagent)
O
-
O
-
Cr
N N
O c) Pyridiium Chlorochromate (Corey’ Reagent)
N
+
H 2
ClCrO
3
d) Pyridinium dichromate
N
+
H
Cr
2
O
7
-
61


Ag
2
CO
3
on Celite

Fatizon Reagent

Solid Support

Mild Conditions

No Acid

No Base

Very Selective

Other functionalities are unaffected

No work-up only filtration.
H
H
C
C H
O
HO H H
H (a) (b)
O
C
AgO
C
O
OAg
AgO
C
OAg
O
AgO
-
C
O
H
+
H
.
OAg
(c)
C
+ 2Ag + CO
2
+ H
2
O
O
2
3

Initial step is reversible adsorption of alcohol on the surface of oxidant

Formation of covalent bond b/w O of OH and Ag +

Second Ag + will convert into Ag by heterolytic cleavage of C-H bond and electron transfer and generation H +

CO
3
-2 pickup H + and converted to carbonic acid which decomposes to
CO
2
and H
2
O
62

63

Ref: A. Mckillop et.al. Synthesis, 401(1979)
F.J. Kakis et.al. J. Org. Chem. 523, 3, 39 (1974)
M.Fatizon et.al. Tetrahedron Lett., 4445 (1972)
Reaction takes place at interface of solid and solution used inert solvent like benzene ith excess of reagent.
O selective i.e. alcohols of different type are oxidized at different rate.
Benzylic or allylic > secondary > primary
Activated alcohols (such as benzylic and allylic alcohols) oxidized faster than saturated alcohols
O O
HO
1 o alcohol
HO
2 o alcohol
OH
AgCO
3
/Celite
Benzene
HO
HO
O
70% allylic alcohol allylic oxidation
1 o alcohol OH O
HO
2 o alcohol
OH
1 o alcohol
AgCO
3
/Celite
Benzene
HO
48%
OH
Primary alcohols are oxidized more slowly than secondary
Highly hindered OH group are unaffected i.e. selectively based on steric crowding.
64

CH
3
OH
CH
3
O
H
3
C H
3
C
AgCO
3
/Celite
Benzene
H
3
C CH
3
OH H
3
C CH
3
OH
Diols behaves differently generally only one OH group is oxidized
O
O
H
CH
2
OH
O
H
O
H
CH
2
OH
Ag
2
CO
3
-Celite
C
6
H
6
, Reflux
O
H
Lctone
O
One of the OH groups being converted to carboxylic acid and predominantly lactone formation takes place.
Other diols (Pir, Sec, e.t.c) give hydroxy ketones.
OH
OH
Ag
2
CO
3
-Celite
C
6
H
6
, Reflux
O
50%
OH
This is an excellent reagent for oxidizing allylic, secondry under essentially neutral conditions.
65


KMnO
4
and MnO
2

KMnO
4
is relatively vigorous oxidant than MnO
2

MnO
2
is mild and more selective

KMnO
4
oxidation of primary alcohol to carboxylic acids is a synthetically useful reaction.
KMnO
4
RCH
2
OH RCHO
RCOOH
HO O
RCH CH
3
RCH CH
3

Usually carried out in the presence of alkali hydroxide

Also performed in buffer

Two phase system containing an aqueous KMnO
4
solution and an immiscible solvent such as C
6
H
6
, ether can also be used.
CH
3
(CH
2
)
6
CH
2
OH
Ag KMnO
4
/ C
6
H
6
CH
3
(CH
2
)
6
COOH
BuN
+
Br, RT

Solid Support KMnO
4
in toluene provides a simple and milder procedure.
(CH
2
)
11 CHOH
KMnO
4
/Alumina
(CH
2
)
11 C O
66

(CH
2
)
11
CHOH + OH (CH
2
)
11
CHO
-
+ H
2
O
O O O
O
H
3
C C H
CH
3
+ O Mn
O
O H O Mn
O
O +
H
3
C CH
3

MnO
4
abstract the α-hydroxy from alkoxide ion either as an atom (or an electron transfer) or as hydride H ion (two electron transfer) But Hydride shift is more reliable.

Permanganate ion is reduced from from Mn(VII) to Mn(V)
2

Useful oxidizing agent for allylic and benzylic alcohols.

Mild and selective than KMnO
4
MnO
20
2 o
/CH
2
Cl
2
C
OH
H O

Neutral solvents are used i.e. benzene, pet. ether, CHCl
3

Simple stirring of alcohol in solvent with MnO
2
for some hours

Used specially prepared MnO
2

MnSO
4
with KMnO
4 in alkaline solution produced very active
MnO
2

This is not clear that actual oxidizing agent is MnO
2
or some other manganese species adsorbed on the surface of MnO
2

C=C bonds and C C remain unaffected by this reagent
HC C C
H
C
H
CH
2
OH
MnO
2
HC C C
H
O
C
H
CH
67


Acid or base sensitive subatrate can easily be oxidized by this reagent
OH
EtOC C C
H
C
H
CHCH
3
MnO
2
O
EtOC C C C
H
CHCH
3
H
3
C
O
S
CH
3
Red
H
3
C
S
CH
3
Dimathyl sulfoxide Dimethyl sulfide

The development of mild oxidant based on dimethyl sulfoxide for the efficient conversion of alcohols to their corresponding carbonyl compounds was a major breakthrough in synthetic organic chemistry.

Wide spread applications

Alcohols to corresponding carbonyl compounds

Tosylate to = = = = = = = = = = = = = =

Halides to = = = = = = = = = = = = = =
 Epoxide to α-hydroxy ketones
Alcohol (CH
3
)
2
S=O + Activation
R'
C
R
Base
H
OH
RR'CO + (CH
3
)
2
S
RCHO + (CH
3
)
2
S Tosylate RCH
2
OTs + (CH
3
)
2
SO
Halide
R'
R
H
C
X
+ (CH
3
)
2
SO RR'CO + (CH
3
)
2
S
68

R R OH
Epoxide HC CH
+ (CH
3
)
2
SO R C
H
C R + (CH
3
)
2
O
O
Arylic tosylate and halide can also convert into their corresponding carbonyl
S compounds.
The commonly accepted gross mechanism
H
H
3
C
S O
H
3
C
+ R
2
C
R
1
X
H
3
C
R
1 H
3
C R
1
S O C R
2
S +
C
H
3
C H
3
C
X
-
H
O
Alkoxy dimethylsulfonium ion
(A key intermediate in all type of DMSO based reagents)
R
2
R
1
= Ar, R
2
= H, X = Br
R
1
= Ar, R
2
= H, X = OTs
R
1
= Alkyl, R
2
= H, X = OTs or halide
H
3
C
H
3
C
S O + E
S O E
H
3
C
H
3
C
H
3
C
H
3
C
S OE + R
2
H
C
R
1
OH
H
3
C
R
1
S O C R
2
+ HOE
H
3
C
H
Alkoxy dimethylsulfonium ion
(A key intermediate in all type of DMSO based reagents)
E = C
6
H
11
N=C=N=C
6
H
11
(DCC)
E = (COCl)
2
(Oxalyl Chloride)
E = Anhydride
69

Decomposition of Alkoxydimethyl sulfonium ion
H
3
C
S
H
2
C
H
R
1
O C
H
R
2
..
B
H
3
C
S
H
2
C
R
1
O C
H
R
2
H
3
C
S
H
3
C
+ O C
R
1
R
2
Alkoxy dimethylsulfonium ion
(A key intermediate in all type of DMSO based reagents)
H
OH H
H
R
O
R
+ (CH
3
)
2
SO
CH
3
R
2
H
B
C C R
CH
3
O S
CH
2
H OH O S
OH O
R
2
C C H
CH
2
R
2
C C + (CH
3
)
2
S
H R H R
In final step formation of a ylid which undergoes intermolecular hydrogen transfer with formation of DMS and a carbonyl compound.
Ref: C.R. Johnson et.al. J. Org. Chem. 32, 1926, (1976)
Various variant of DMSO-based oxidants are available
In some cases formation of thio ether are also reported through following mechanism.
70

H
3
C
H
3
C
S O + E
H
3
C
S
H
3
C
O E
- H
H
3
C
R
1
R
2
CHOH
S
+ HOE
H
2
C
Methylene Sulfonium Ion
H
R
1
C OCH
2
S CH
3
R
2
Thioether
Different combination of DMSO with activators or electrophoiles
1.
DMSO-N,N’-Dicyclohexylcarbodiimide (DCC) (Commonly known as
Pfitzer-Moffatt Reagent)
2.
DMSO-(COCl)
2
(Swern Reagent)
3.
DMSO-(CH
3
CO)
2
O
4.
DMSO- (CF
3
CO)
2
O
5.
DMSO-SO
3
6.
DMSO-P
2
O
5
7.
DMSO-Cl
2
This is one of the best methods of oxidation. In this oxidation oxalyl chloride is used as activator.
By reaction of DMSO and oxalyl chloride followed by treatment of the resulting alkoxy sulfonium salt with a base, usually triethylamine, a wide variety of alcohols has been converted into corresponding carbonyl compounds in high yields.
71

OH
HOH
2
C
O
O
O
O
O
DMSO, (COCl)
2
CH
2
Cl
2
, Et
3
N
DMSO, (COCl)
2
CH
2
Cl
2
, Et
3
N
O
H
OHC
O
O
O
O
O
High yield, mild conditions, by-product easily separable
H
3
C
S
H
3
C
O + (COCl)
2
CH
2
Cl
2
, -60 o
C
H
3
C
S
H
3
C
O
O O
C C Cl Cl
H
3
C
S
H
3
C
Cl
RCHOHR'
H
3
C
S
H
3
C
O
R
C
H
R' base
H
3
C
S
H
2
C
O
R
C R'
H
R
C
R'
O + H
3
C S CH
3
A number of methods for oxidation primary and secondary alcohols to aldehyde and ketone by the action of base on the derived alkoxy sulfonium salts differ from
72

each other mainly in the way in which the alkoxy sulfonium salt is obtained from the alcohol.
One of the earliest procedure involved reaction of alcohol with dimethylsulfoxide and dicyclohexyl carbodiimide (DCC) in the presence of proton source.
R
1
CH OH
R
2
C
6
H
11
N=C=N-C
6
H
11
(CH
3
)
2
SO, H
3
PO
4
, 75 o
C
R
1
R
2
O
C
6
H
11
N=C=N-C
6
H
11
+
H
3
C
S O
H
3
C
H
C
6
H
11
NH-C=N-C
6
H
11
O R
1
CHOHR
2
S
H
3
C CH
3
H
3
C
S
H
3
C
+
O
C
H
R
1
R
2
Base
H
3
C
H
2
C
S
H
O
C
H
R
1
R
2
R
1
R
2
O + (CH
3
)
2
S
(C
6
H
11
NH)
2
CO dicyclohexyl urea
The oxidation with DMSO, DCC also known as Pfitzner-Moffat oxidation.
A disadvantage of this route is that the product to be separated from the dicyclohexyl urea formed in the reaction.
73


Primary and secondary alcohols to ketone

Aluminium alkoxide + carbonyl compound

Reverse of Meerwein-Pondroff-Verley Reduction

Useful in the field of steroids.

Al(i-PrO)
3
, (Al(t-BuO)
2
, Al(PhO)
3

Carbonyl compounds include butanone, benzoquinone, benzophenone, flournone.

Flourenone is advantageous due to considerably short time and temperature of reaction
 α-hydrogen containing carbonyl compounds under alkaline conditions undergo self condensation

Use of inert solvent suppresses self condensation.

Benzene-acetone and toluene-cyclohexane are commonly used solvents, however, toluene-cyclohexane reduces the time of reactions.

Use of flourenone as hydride ion acceptor often reduces the temperature up to room temperature.


Use of 1-methyl-4-piperidone as the hydride acceptor allow the easy removal of excess oxidant and corresponding alcohol at the end of reaction by only washing with aqueous acid.
74


Exchange of alkoxide

Hydride transfer from alkoxide to carbonyl

Pseudocyclic intermediate formation
R
1
R
2
O + H
3
C
OH
C CH
3
H
Al(OR')
3
R
1
R
2
O + H
3
C
H
C
O
CH
3
+ HOR'
Al(OR')
2









R
1
H CH
3
R
2
O
Al
R'O
O
OR'
CH
3
H
3
C
H
3
C
O +
Crystalline solid
Decomposes at 140
°
C
R
1
H
C
O
R
2
Al(OR')
2
Used in Acetic acid or Benzene for Oxidation
Widely used for Oxidative cleavage of 1,2-diols, α-hydroxyl ketones, 1,2diketones and α-hydroxy acids
Oxidation carried out usually at or near room temperature
At elevated temperature the oxidative power dropped considerably
Acetic acid is usual solvent for Oxidation
Other solvents including Benzene, CH
2
Cl
2
, CHCl
3
, trichloroethane,
1,4-dioxane, ethylacetate, cyclohexane, nitrobenzene and CH
3
CN are also used.
The mechanism aspects of 1,2 diols cleavage with lead tetraacetate are as follows
75



The preferred mechanism for lead tetraacetate cleavage of a diols involves a cyclic transition state.
An alternate cyclic mechanism involves coordination of one hydroxy group to lead atom followed by interamolecular proton transfer
R
2
CH OH
Pb(OAc)
4
R
2
CH OH
CH
3
CO
2
H
2R
2
CO + Pb (OAc)
2
R
2
CH OH
+ Pb (OAc)
4
R
2
CH OH
R
R
C O
R C
R
OH
Pb (OAc)
3
+ HOAc
(R)
2
C
O
C
(R)
2
O
H
Pb(OAc)
2
O
O C
CH
3
2RC O + Pb(OAc)
2
+ CH
3
CO
2
H

In trans diols which cannot rapidly generate a cyclic transition state. The intermediate (b) breaks down with a proton transfer to a base.
R
H
R C
O C
H
(b)
B:
O
R
2
Pb (OAc)
2
OAc
2R
2
CO + Pb(OAc)
2

The oxidation of cyclohexan-1,2-diol is acid catalyzed
76


A strong acid e.g. H
2
SO
4
is a better catalyst.

Acid could catalyze the reaction in various ways.

It could protonate lead tetraacetate and increases the rate of co-ordination to the diol or it could catalyze the ring closure or its direct decomposition to product.
Pb(OAc)
4 +
H
+
Pb(OAc)
3
R
2
C
R
2
C
+
OAc
H
OH
+ Pb(OAc)
3
O
+
AcH
OH
R
2
R
2
C
C
H
O Pb(OAc)
3
OH
R
2
R
2
C
C
O
O
Pb(OAc)
2
R
2
R
2
C O Pb(OAc)
2
C OH
O
H
+
Ac
2R
2
CO
 Lead tetraacetate also cleaves α-hydroxy acids

Various mechanisms are proposed for this cleavage.

One involves co-ordination of hydroxy group to lead atom, followed by the loss of carbon dioxide

Secondly co-ordination of both hydroxyl and carboxyl to the lead followed by the decomposition of cyclic intermediate.
77

R
H
H
C
CO
2
H
OH + Pb(OAc)
4
R C O
O
C
RCHO + Pb(OAc)
2
+ HOAc + CO
2
O
H
Pb(OAc)
2
OAc
R
2
H
C O
O C O
Pb(OAc)
2
RCHO + CO
2
+ Pb(OAc)
2
78


Solutions of periodic acid KIO
4
, NaIO
4
in aq. or aq. organic media

Co-solvents used methanol, ethanol, t-butanol, 1,4-dioxane, THF, DMF and acetic acid.

Co-solvents used less than 50% of the reaction media.

Primary use is the cleavage of 1,2-diols, 1-amino-2-hydroxy compounds, α- hydroxy ketones, 1,2-diketones.

Useful method for water soluble poly-functional compounds such as carbohydrates and certain amino acids.

For water-insoluble compounds Pb(OAc)
4 is preferable.
O
O
I
O
O
K
+
or Na
+
O
O
HO
I
OH
OH
H
3
C (CH
3
)
7
Periodic salt
H
C
OH
H
C CH
3 +
O
OH
O
I
O
O
Periodic acid
R
H
C
H
C CH
3
O
I
O
O
O
OH
OH
Periodic acid
H
RCHO
+ H
3
CC O +
O
I O
O
R
H
C
H
C CH
3
O
O
I
O
O
O
79

O
R C H
H
2
CrO
4
RCOOH
Mechanism
O
R C H + H
HCrO
4
OH
R C H
O CrO
3
H
RCOOH + HCrO
3
KMnO
4
Oxidation
C
6
H
5
O
C H
KMnO
4
H
3
O
C
6
H
5
COOH
Mechanism
C
6
H
5
C
6
H
5
O
C H + H
3
O H
2
O +
C
6
H
5
CH
MnO
4
OH
H
C
OH
O MnO
3
C
6
H
5
CO
2
H + MnO
3
Chromic Acid:
Cleavage of C-C bond
O
H
2
CrO
4
HO
2
C(CH
2
)
4
CO
2
H
80

O
H
OH
H
2
CrO
4
H
O
O CrO
3
H
O
O
+
HO
Cr
O
HO
O
OH
O
CrO
2
OH
O
Mechanism
HO
2
C(CH
2
)
4
CO
2
H
O
CH
3
CH
2
C CH
2
CH
3
H
3
C
OCOCH
3
C
H
C
O
CH
2
CH
3
+
H
3
C
OCOCH
3
C
H
C CH CH
O OCOCH
3
3
81

H O
OAc H O Pb(OAc)
2
H
3
C C
H
C CH
2
CH
3
+
Pb(OAc)
3
H
3
C C C CH
2
CH
3
OAc
OCOCH
3
OCOCH
3
H
3
C C
H
C CH
2
CH
3
+ H
3
C C
H
C CH CH
3
O O OCOCH
3
31% 7%
In sterically hindered enols, the acetoxylation procedure is accompanied by a rearrangement.
CH
3 CH
3
CH
3
Pb(OAc)
4
O
Attack by
OAc
O
CH
3
(AcO)
2
Pb O
OAc
CH
3
CH
3
Rearrangement
CH
3
Shift
- H
+
CH
3
OAc
CH
3
+
O
H
O
CH
3 CH
3
82


Peroxy acids are used as Oxidants.

Ketones to Ester or Lactones.

Organic peroxy acids i.e, MCPA, Per acetic acid, trifluoroacetic acid give better results.

Mild Conditions.

Applicable to open chain, cyclic and aromatic ketones.

Used to prepare medium and large ring lactones which are difficult to prepare.

With unsaturated ketone mixture of products results through competing attack at C—C double bond

A new reagent bis(trimethylsilyl)peroxide Me
3
SiOOSiMe
3
eliminate this difficulty, it behaves as masked H
2
O
2
and in the presence of cat.
Trifluoromethylmetane sulfonate. It does not affect the double bond.

Reaction takes place trough a concerted intermolecular process.

Migration of a group from carbon to electron deficient oxygen.

In the presence of strong acid, ketone protonated and addition of peroxy acid to ketone.
O
O
O
MCPBA
Mechanism
83

O OH
H
..
OH
O O
O
C C
2
H
5
+
C
2
H
5
O
..
C O OH
O
O

Interesting reaction of RuO
4
.

Oxidation of aliphatic ethers to esters or lactones in case of cyclic ethers.
RuO
4
O O
O

It is used under mild conditions.

Reaction stops after first oxidation.

Esters or lactones cannot oxidize with RuO
4
.

So attempt prepare succinic anhydride by this way were failed.
RuO
4 RuO
4
O O O O
O
O
84

 A mechanistic study proposed that a hydride from α-position of ether shift to
RuO
4
, then HRuO -
4 attacks on the carbonium ion, whish is generated on the
α-position of the ether and oxidation takes place.
Mechanism of RuO
4
Oxidation
O
H
+ Ru
O
H
O
O
O
O
+
H
+
HO
Ru
O
O O
OH
O
+ H
2
RuO
3
Ru
O
H
O O
O
The formation of 2,5-hexadione by oxidation of 2,5-dimethyl tetrahydrofuran can also be explained by hydride transfer mechanism.
85

H
3
C
H
O
H
3
C
O
Ru
O
CH
3
+ Ru
H
O
O
O
CH
3
H
3
C
H
H
3
C
O
O
-
O
H
O
+
HO
CH
3
+
Ru
-
O
H
O
O
O
OH
Ru
O
O
O
OH
+ H
2
RuO
3
O
O
86

These are very sensitive to oxidation and generally darken on exposure to air, through auto-oxidation at the surface, to give mixture of complex products.
Synthetically useful methods have therefore to be highly selective. The most successful reagents are hydrogen peroxide and per acids.
Hydrogen peroxide converts primary aliphatic amines into aldoxime.
n-C
3
H
7
CH
2
NH
2
H
2
O
2 n C
3
H
7
CH NOH
An Aldoxime
R CH
2
NH
2
+ O OH -H
2
O
RCH
2
NH H
2
O
2
RCH
2
N(OH)
2
-H
2
O
RCH
H
OH
Oxidation of aromatic amines resulted in formation of nitroso compounds.
Perdisulphuric acid HO
3
S-O-O-SO
3
H is used as an oxidant.
NH
2 NO
NO
2 NO
2
HO
3
S-O-O-SO
3
H
NOH
o- Nitrosonitro benzene
87

Primary and secondary nitroalkanes play an important role in organic synthesis because of their ready transformation into carbonyl compounds.
R CH R'
RC R'
NO
2
O
Reaction of nitro compounds with base, α-proton is abstracted leads to the formation of resonance stabilized nitronate anions which than hydrolyzed and give a carbonyl compounds.
O
R
'
R
"
CH
+
N
:B
R
'
R
"
C N
O
H
+
O
O
R
'
R
"
C N+
OH
O
-
R
'
R
"
C
N+
OH
H
+
O
O H
R
'
R
"
C N+
OH
H
2
..
O
OH
R C
N
HO
Reference

Hawthorne, J.Am.Chem.Soc. 1957, 79, pp.2510.

Thicde, Ibid. 1952, 74, pp.2615.

Folliard, Tetrahedron, 1971, 27, pp.323.
OH
R"
R'
O
C
R"
88

Azo compounds may be oxidized to azoxy compounds by per acids.
Ar N N Ar
CH
3
COOOH
Ar N N
O
Ar
Ar N Ar
Ar N
OH
N Ar
O
CH
3
C O OH
Ar N N Ar
O
Isocyanides have been oxidized to Isocyanates with HgO and with O
3
as well as halogen and DMSO. Mechanism involves formation of R-N=CCl
2
which hydrolyzed to Isocyanates.
Cl
2
R N C
R N C O
Me
2
SO, H
2
O
Mechanism
R
N
+
C
-
Cl Cl R N
+
CCl
Cl Cl
R N C
Cl
Cl
R
N
Cl
C
O H
R N C O
HOH
89

A more powerful oxidant than hydrogen peroxide converts primary amines directly into nitro compounds. The yield with aromatic amines are generally high e.g onitroaniline is oxidized in refluxing CH
2
Cl
2
to o-dinitro benzene in 92% yield.
NH
2
NO
2
NO
2
NO
2
CF
3
CO
3
H
With aliphatic amines, however, yields are low. Other oxidants have been used with moderate success e.g. n-hexylamine is oxidized in 33 % yield to the nitro compounds by peracetic acid.
Oxidation of secondary amines with H
2
O
2
gives hydroxylamine.
R
2
NH
H
2
O
2
R
2
N OH + H
2
O
Tertiary amines with H
2
O
2
give their N-oxide hydrates, by nucleophilic displacement as in primary amines. The N-oxides is obtained by warming the hydrate in vacuo.
R
3
N
H
2
O
2 R
3
N OH + OH
Aromatic amines behave similarly e.g. pyridine.
Heat
R
3
N O
90

The rearrangement of oxime to amide under the influence of acid, Lewis acid is termed as the Beckmann Rearrangement.

Commonly H
2
SO
4
, PCl
5
in Et
2
O, poly phosphoric acid, aryl sulfonic halides,
HCl in HOAc and Ac
2
O.

HCl in HOAc and Ac
2
O is useful if the starting oxime is insoluble in other medium.
R
1
C R
2
H
+
N
OH
R
2
C NHR
O
Mechanism
R
1
C R
2
H
+
N
OH
R
1
C R
2
-H
2
O
N
+
OH
2
R
2
+
C
R
2
C NHR
1
O
N R
1
H
2
O
R
2
C
+
OH
2
N R
1
R
2
C
-H
+
N R
1
O H
91

The acid catalyzed reaction of hydrazoic acid with carboxylic acid to give amines with ketones to give amide and aldehydes to give nitriles are all known as Schmidt reaction. The mechanism of reaction with ketone has similarities with Beckmann rearrangement.
Ketone
O
HN N N
-
R" C R'
H
+
R" C R'
HN
3
R" C R'
O H
+
O
H
N N
+
N
-
R" N CR'
-H
2
O
R" C R'
-N
2 R" N C
+
R
'
..
H
2
O
OH
2
-H
R" N
H
CR'
O
R" N CR'
O H
-H
+
H
O
R C
H
OH
R
N
HN
3
-H
2
O
R
C O
N
O H
C O
O
O
R C
+
H
R
OH
2
N N
-H
2
O
N
R
C O
..
H-O-H
C
RNH
2
+ CO
2
N
+
N
+
H
N
-
92

Pb(OAc)
4
(C
6
H
5
)
3
C-NH
2
C
6
H
6
, heat
(C
6
H
5
)
2
-C=N-C
6
H
5
Mechanism
H
(C
6
H
5
)
3
..
C-NH
2
Pb(OAc)
4
(C
6
H
5
)
3
C-N-Pb(OAc)
2
(C
6
H
5
)
2
-C=N-C
6
H
5
O
CH
3
C=O
(C
6
H
5
)
2
C-N
C
6
H
5
C
7
H
15
CH
2
I + (CH
3
)
3
N-O
CHCl
3
heat
C
7
H
15
CHO
Mechanism
H
C
7
H
15
CH
2
-I + (CH
3
)
3
N-O C
7
H
15
C
H
O N(CH
3
)
3
C
7
H
15
CHO
Aldehyde
93

H
2
O
2
2RSH RSSR
Thiols are easily oxidized to disulfides. Many reagents are used to convert them into disulfides. Oxygen in the air oxidizes thiols on standing, if a small amount of base is present.
RSH +Base
H
2
O
2
RS + O
2
RS + BH
RS + O
2
RS + O
2
RS + O
2
-2
2RS
O
2
-2
+ BH
RSSHR
OH + B + O
2
J. Org. Chem. 1963, 28, 1311.
Oxidation of thioethers to sulfoxides and sulfones.
O
R-S-R
H
2
O
2
R-S-R R-S-R
O
Sulfoxide
O
Sulfone
R-S-R + H-O-OH
R-S-R
..
+ H-O-O-H
O
R-S-R + OH
O
O
H
R-S-R
O-OH
Tetrahedron Lett. 1963, 1479.
Ibid, 1966, 1127.
Ibid, 1980,3213,
J. Chem. Soc, Perkin Tran 2, 1978, 603
J. Chem. Soc, Chem. Commun. 1983, 1203.
O
R-S-R
R-S-R + H
2
O
O
O
94