Oxidation 97

3.7. Pyridinium Chloro Chromate (PCC):

+ – O O
+ HCl + CrO3 + Cr
N O N Cl O
O
Cr H
Cl O
PCC is a very important oxidising reagent which will give controlled oxidation in the case of primary alcohol.
It does not give over oxidation during the oxidation of primary alcohol.
It does not oxidised t-alcohol. But in the case of 3º–allylic alcohol having atleast one  -hydrogen
through [3, 3] sigma tropic rearrangement. PCC will give oxidation with the migration of double bond.
PCC
R CH2 OH R CHO No over oxidation
or PCC/CH2Cl2
R R
PCC
OH O
or PCC/CH2Cl2
R R

Me Me
OH

PCC

O
[Oxidation through 3, 3 STR]

Acid catalysed oxidation of alcohol with double bond present in the compound, by PCC cyclization
takes place.
Me OBn Me OBn

PCC/CH2Cl2
Me HCl
OH Me OH Me
Me
If PCC reagent is used with buffer solution such as NH4Cl/H2O (Buffer), NaH2PO4/Na2HPO4,
NaHSO3/H2O, (CH3COO– Na+) (Buffer) then no acid catalysed cyclization or no any acid catalysed
reaction will occur.
Me OBn Me OBn

PCC/CH3COO–Na+
Me Me
OH Me O Me
In 1, 4 diols or 1.5 diols PCC reagent is used then it will give controlled oxidation and form cyclic ester
or lactone ring.
O
HO HO

OH PCC
O
OH
HO HO
98 Oxidation
Example:
OH O

1.5 eq., PyH+CrO3Cl–

t-BuMe2SiO Me t-BuMe2SiO Me
Me Me

t-BuOCO t-BuOCO

O O
1.4 eq. (PyH+)Cr2O72–
HO OEt O OEt

3.8. Pyridinium Dichromate (PDC):

O O

Cr Cr
O O O
N
O O
H
PDC is soluble in H2O, DMF and DMSO but sparingly soluble in CH2Cl2 or CHCl3. The reagent is less
acidic than PCC. Hence, oxidation in CH2Cl2 can be carried out under nearly neutral conditions. This
permits the conversion of primary alcohol containing acid sensitive group into the corresponding alde-
hyde or ketones.
H
O PDC O
OH CH2Cl2 O

In DMF solution however PDC oxidizes non-conjugated primary alcohol to corresponding carboxylic
acid and in CH2Cl2 to give aldehyde.

PDC PDC
COOH CHO
DMF CH2Cl2
OH

In carboxylic acid solvent, PDC oxidizes primary alcohol to anhydrides and in the presence of liq. NH3
convert into amide.
O O O
PDC/liq. NH3 PDC/AcOH
R CH2OH
C R C O C CH3
R NH2
R PDC R
OH any solvent O
R R

3.9. Collins-Ratclifte Reagent:

+ CrO3 + CH2Cl2
N
Oxidation 99
Collins reagent is a mild reagaent for the oxidation of alcohols that contain acid sensitive groups. Collins
reagent prepared by adding CrO3 to a mixture of pyridine-CH2Cl2.

–18ºC
CrO3 + [CrO3.Py2]
CH2Cl2
N
Collins reagent primary alcohol oxidised to aldehye and secondary alcohol to ketone respectively.
collins reagent
RCH2OH R CHO

R R
collins reagent
OH O

R R

OH O
(a) CrO3, pyridine, CH2Cl2
O (b) Add alcohols substrate O

(c) work up
O H O H
90%
3.10. Jones reagent:
CrO3  H 2SO 4  H 2O  acetone
Or, Na 2Cr2O7  H 2SO 4  H 2O  acetone
Oxidation of primary alcohols with Jones Reagent may result in the conversion of the aldehyde initially
formed to the corresponding carboxylic acids.
CrO3/H2SO4
R CH2OH acetone R COOH

OH O
Jones reagent
acetone

OH O
Na2CrO7, H2SO4
H2O, Et2O, r.t.

Jones reagent used for the oxidation of primary and secondary alcohols and does not effect any group
present in the compound.
OH O

Jones reagent

OH O
100 Oxidation

3.11. Swern Oxidation:

DMSO   COCl  2  CH 2Cl2
Activation of dimethylsulfoxide (DMSO) by oxalyl chloride produce intermediate (A) that decompose
rapidly at –78ºC to furnish chlorodimethylsulfonium chloride (B) along with CO and CO2. Reaction of
(B) with RCH2OH (or R2CHOH) leads to intermediate (C), which upon addition of Et3N and warming
afford the corresponding carbonyl compound Me2S, Et 3 NH  Cl

Me Me
(COCl)2 O
Me2SO S O Cl–
–CO S Cl Cl–
CH2Cl2, –78ºC
–CO2
Me Cl Me
O (B)
(A)
O Me
Me
Add base S O R RCH2OH
H R S O R
Et3N warm Me –78ºC
H2C H
+ Me2S H H
+ Et3N.HCl H

DMSO/(COCl)2/–60ºC
R CH2OH R CHO
Et3N
[1º-alcohol]
R DMSO/(COCl)2/–60ºC R
CH OH C O
R Et3N R

OH O

(a) DMSO (COCl)2

H
CH2Cl2, –50ºC
(b) Et3N, –50 to 0ºC
(c) H2O workup

OH O O
Swern Ph3P = CHCO2M
OH O
n-C6H13 [O] n-C6H13 –78ºC to 20ºC n-C6H13 CO2Me

H
–
If base is not present then Nu substitution will occur at the end of reaction and swern substition will
occur.
DMSO/(COCl)2/–60ºC
R CH2OH R CH2Cl
then 0–50ºC
Nucleophilic substitution
R R
DMSO/(COCl)2/–60ºC
OH CH Cl
then, 0–50ºC
R Swern substitute R
Oxidation 101

Me Me Me Me
O O DMSO, (COCl)2 O O
CH2Cl2, –78ºC
Me then Et3N Me CHO
OH

Me Me
Swern reagent can also be used for the oxidation of primary amide substrate into nitrile or cyanide.
O

C DMSO/(COCl)2/–60ºC
R NH2 R C N
Et3N
1º amide Nitrile

O O C N
HO DMSO/(COCl)2/–60ºC
C
NH2 Et3N
O
HO
3.12. Moffatt oxidation: [DCC/DMSO]
DCC/DMSO
R CH2OH R CHO
R R
DCC/DMSO
CH OH C O
R R
DMP/CH2Cl2
R CH2 OH R CHO
R R
DMP/CH2Cl2
CH OH C O

R R
Mechanism:

H CH O
OAc OAc
AcO R
OAc OAc
I I O
AcO
+ HO CH2 R C
AcOH R H
O O
OH O
IBX(2.5) eq.
DMSO
OH O
OH

OH IBX(2.2) eq.
O
OH DMSO
102 Oxidation

O O
O O
DMP(1.3 eq)
CH2Cl2, 0ºC
OH O
MeO MeO

C5H11 C5H11

HN HN
1.5 equivalent
CH2Cl2, room
temperature
C4H9 C4H19

OH O

When dicyclohexyl carbodiamide reagent is mixed with DMSO oxidizing reagent then it is specially used
for the oxidation of steroidal alcohol.

BnO Me
BnO Me

Me
Me DCC/DMSO

O
HO

Me
Me

Me
Me

Me
Me
HO DCC/DMSO
O

HO
O

O O O O
Oxidation 103
3.13. Dess-Martin Periodinane:
DMP-Oxidation
O O
O O OAc
COOH O
I OAc
I I
Oxone Ac2O
OAc
OH
H2O, 70ºC TsOH(cat.), 80ºC

DMP
IBX
It is a hypervalent iodine based oxidising reagent which is highly specific for the oxidation of primary and
secondary alcohol and does not effect any sensitive functional group.

OH H
O

1 eq. IBX
DMSO, r.t.
N
H N
H

3.14. Tetrapropylammonium Perruthenate (TPAP):

Pr4NRuO4
TPAP is an air stable oxidant for primary and secondary alcohols. It is used in catalytic amount in the
presence of a Co-oxidant such as N-methylmorpholine-N-oxide (NMO).
TPAP(cat.)
R CH2OH RCHO + Ru(IV)
NMO

O O
Ru(IV) + Ru(VII) +
N N
Me O
Me
NMO
TPAP tolerates a wide variety of functional groups including double bonds, enolates, halides epoxides,
esters, and lactones. Protecting groups such as MEM, trityl, silyl and benzyl ethers, THP and acetals are
not effected.
O

Me Me
HO H
TPAP (5 mol%)
O O
NMO (1.5 eqi.)
molecular sieves
OTBS (500 mg/ mmol) OTBS
CH2Cl2 (2mL/mmol)
104 Oxidation
Mechanism:

O
O O
O O H
R CH2 OH + Ru R CH O Ru C
O R H
O O
O H +
O O O
O O O Ru
O O
Ru O Ru O
Ru OH
O O ••
O N O H
O + ••
••
O
N N O

Examples:

O
HO

O O
TPAP/NMO TPAP
DCM/MeCN
OH OH

O O O Lactone

OBn OBn
Me Me

t-BuPh2SiO cat. TPAP, NMO t-BuPh2SiO

MeCN, 25ºC
OHC
O O
OH
O O

3.15. Activated Manganese Dioxide(MnO 2):

 MnO 2  ppt 
MnCl2  KMnO 4  H 2 O 
MnO2 is highly chemoselective oxidant-Allylic, Benzylic, and propargylic alcohols are oxidised faster
than saturated alcohols. The oxidation takes place under mild condition in H2O, acetone and CHCl3.
OH O
MnO2
OH acetone OH
(i)
Oxidation 105

H H

O O

MeO MnO2 MeO

OH acetone OH
(ii)
CHO

OH

HO Ph O Ph

MnO2
OH O
(iii) C

H
HO OBn HO OBn

Boc Boc
O N 10 eq. MnO2 O N
(iv) Ph3P = CHCO2Me CO2Me
OH
CHCl3, reflux
KMnO4 (absored on a solid support) and useful alternative to MnO2 in the oxidation of allylic or benzylic
alcohol.

3.16. Silver carbonate on Celite ‘ Fetizon’s reagent’:

 Ag2CO 3 + Celite
Fetizon’s reagent will give chemoselective oxidation of secondary alcohols in the presence of primary
alcohols.
Ease of alcohol oxidation:

Allylic  Benzylic – OH  2º OH  1º OH  less hindered   1º OH

OH O
Ag2CO3/celite
OH Benzene OH

OH OH

Ag2CO3 (5 eq)
OH O

OH OH
Oxidation of 1, 4 or 1, 5 alcohols to gives 5 or 6 membered lactones respectively.
O
OH Ag2CO3 (10 eq)

OH Celite, benzene, reflux

O
106 Oxidation

H O

O O
OH Ag2CO3 on celite
O
OH PhH, reflux
O O

Me Me
3.17. 2, 2, 6, 6 Tetramethyl 1-Piperidinyloxy (TEMPO) Me N Me
O•

TEMPO is a commercially available nitroxyl radical-containing reagent that catalyses the oxidation of
primary and secondary alcohol. TEMPO primary alcohols are oxidised faster than secondary.
TEMPO
R CH2OH R CHO
CH2Cl2

R R
TEMPO
OH O
CH2 Cl2
R R

OH OH H
TEMPO
R OH CH 2Cl2 R O
OH OH

OH
H 2O
R CHO R R COOH
OH +
N
_
O X

NaOCl, NaBr, CH2Cl2, H2O CHO

Ph OH Ph
TEMPO (Cat.)
NHCbz 0–5ºC NHCbz

HO OH O OH

TEMPO, O2 H
O O
CuCl, DMF

TBS O O TBS O O

t-BuOCO OH t-BuOCO OH

Me OH 1 mol % TEMPO Me
CH2Cl2, –5ºC CHO
NaOCl
N OH N HO
Ph2C Ph2C
Oxidation 107

3.18. Ceric Ammonium Nitrate (CAN):

Chemoselective oxidation of a secondary OH group in the presence of a primary OH group has been
achieved with (NH 4)2Ce(NO3)6, NaBrO3. CAN does not affect any double bond present in the group.
(NH 4)2Ce(NO3) 6
R CH2 OH R CHO

R R
CAN O
OH
R R

OH O
H
CAN
R OH R O

OH O

HO OH O OH
(NH 4) 2Cl (NO 3) 6
NaBrO3
CH3 CN, 80ºC

OMe O

CAN
THF, H2 O

OMe O

3.19. Sodium Hypochlorite (NaOCl):

Chemoselective oxidation of a secondary OH group in the presence of a primary OH group is possible with
NaOCl in aqueous acetic acid.

CH2 CH2 OH O
aq. NaOCl
CH3 CH CH2 CH3
(1.05 eq)
OH ACOH OH H

OH O
Aq. NaOCl
OH OH
(1.05 eq)
ACOH

NaClO2
R CHO R COOH
H2O2 , MeCN
H 2O, NaH2 PO4
108 Oxidation

3.20. Selenium Dioxide:

SeO2, SeO2 / ACOH, SeO2 / H2O, SeO2 / ACOH–H2O
SeO2 is specially used for the oxidation of allylic carbon, having atleast one allylic hydrogen into allylic
alcohol. Mechanism based on following pericyclic reaction.
(i) Ene reaction
(ii) [2, 3] Sigmatropic shift
SeO2
R CH CH CH3 R CH CH CH2OH

Mechanism:

O O
Se
O OH
H
SeO2 Se
(i) R CH CH CH2
Ene reaction CH
R CH CH2

2
CH O
H O 1 O R CH CH2 Se
Se [2, 3] Sigmatropic shift
OH
(ii) OH2
CH
1
R CH CH2
2 3 R CH CH CH2OH + Se(OH)2

Selenium dioxide exhibits a useful stereochemistry in reaction with trisubstituted gem-dimethyl alkenes. The
products are always predominantly the E-allylic alcohols.
In this reaction the methyl group trans to main chain will react rather than the cis, thus only one (E) isomer
is formed.
H3C Et H3C CH2CH3 H3C CH2CH3
SeO2 SeO2
excess
OHC H H3C H HOCH2 H

Tri-substituted alkenes are oxidised selectively at the more substituted end of C–C double bond including
that the ene reaction is electrophilic in character. Tri-substituted alkenes are preferentially oxidised at one
of the allylic group at the di-substituted carbon.
H3C H HOCH2 H
SeO2
C
H3C CH3 H3C CH3
When double bond is in the ring, oxidation whenever possible occurs with in the ring and again  to more
substituted end of the double bond. (Indicate that ene reaction electrophilic in nature).

 CH2 CH3 CH2 CH3

 HO
SeO2
t-BuOOH
Oxidation 109
In the case of terminal alkenes, allylic rearrangement takes place

OH
SeO2
CH3 CH2 CH CH2 CH 3 CH CH CH 2 (Normal product)
+
CH 3 CH CH CH2 OH (Rearrangement product)

Oxidation of alkynes:
SeO2 with small amount of conc. H2SO4

O O
+
SeO 2, H
R C C R R C C R

O O
+
SeO2, H
H C C R H C C R

+
SeO2, H
CH 3 C C H CH 3 C C H

O O

+
SeO2, H
Ph C C Ph Ph C C Ph

O O
Mechanism:

R C C R R C C R R C C R + Se

O O O O
O Se O
Se

Oxidation of Carbonyl Compound:

SeO2 oxidises  -carbon of carbonyl group. This oxidation can only be possible if carbon has at least two
hydrogen.
O O O
SeO 2, 89ºC
R CH 2 C R R C C R
H 2O/ACOH
O O
SeO 2, 89ºC
R C C R
Dioxane
Mechanism:
If water present
OH
SeO 2 + H2O O Se
OH

H H H O O
R C C R R C C R R C C R R C C R + Se + H2O
O H O O O

HO HO Se O Se
Se O
OH HO
110 Oxidation

In absence of water:

H H O H
R C C R R C C R R C C R

O H O Se OH
H O
Se O
O –H2O

O H
OH2
R C C R R C C R R C C R

O O O Se O Se
+ H2O + Se OH O

SeO 2
(i) Ph CH2 C Ph Ph C C Ph

O O O

O O O
SeO2
(ii) CH 3 CH2 C CH3 CH3 C C CH3

Note: Reactivity order

[ CH 2 > CH3 > CH]
Reactivity of CH2 group is more than CH3 group. Because enolization of methylene group occurs more
readily than methyl group.
SeO2
CH3 CHO CHO CHO

O O
SeO2
CH 3 C CH 3 CH3 C CHO

SeO2

N CH3 N CHO
-Picoline

O O
SeO2

O
Oxidation 111

CO2Et CO2 Et
SeO2
O
CO2Et CO2 Et

O O

CH 3 SeO 2 CHO

O O
SeO2

O
O O

SeO2
O

O O

SeO2/NaOCOCH3
COOMe COOMe
CH3COOH/H2O/30ºC
O O O
O
H

Dehydrogenation:
SeO2 used to dehydrogenate 1, 4-dicarbonyl compound and 1, 2 diarylethane.
O O O O
SeO2
R C CH2 CH2 C R R C CH CH C R

SeO2
Ar CH2 CH2 Ar Ar CH CH Ar
Mechanism:

O H O O H O

R C CH CH2 C R R C CH CH2 C R

Se
O OH
OH

O O O H O

Se(OH)2 + R C CH CH C R R C CH CH C R

Se
O OH
112 Oxidation

O O O O
SeO 2
(i) Ph C CH2 CH2 C Ph Ph C CH CH C Ph

CH2 COOEt SeO 2 CH COOEt

(ii)
CH2 COOEt CH COOEt

Acetic acid undergoes dehydration to give succinic acid

COOH
SeO 2
2CH3COOH succinic acid

COOH
O H

HO C CH2 O
O H O
CH2 C OH
CH2 C O H CH2 C OH
CH2 C OH
Se Se
O O O
O OH

SeO2

O O
O O
H

Hydrated form of SeO2:

H
O H _
O O HO
–
O –H2O [2, 3] –SeO
Se + Se
+ Se STR
Se HO H O
O HO
HO OH H

* E-Selectivity:

0.5 Mol SeO2

95% C2H5OH
Reflux HOH2C

H
–H2O R OSeOH
Se
R Se O O
H OH R
H HO OH

“R must be equatorial” in the above transition state. When there is no allylic hydrogen in the substrate then
oxidation of only C = C occurs as shown below
Oxidation 113
H H
R C C R R CH CH R R C C R R C C R
H H
O O O O O O –H2, –Se O O
Se Se Se -dicarbonyl compound

* The alcohols that are initial product can be further oxidized to carbonyl group by SeO2, and the
conjugated carbonyl compound is usually isolated. If the alcohol is the desired product, the oxidation can
be run in acetic acid solvent in which acetic ester are formed.
CH3 CH3 CH3 CH3

SeO2
+ +
CH3COOH
AC2O Complex O2CMe O
CH CH CH CH
Me Me Me Me Me Me Me Me
35% 18% 8%
3.21. N, N–Dicyclohexylcarbodiimide (DCC):

N C N

+ –
C6H11 N C N C6H11 C6H11 N C N C6H11
Introduction: DCC is a powerful dehydrating agent are stored under anhydrous conditions. It is commercially
available as a waxy low melting solid, which melt at 34–35ºC.
Preparation: (i) By oxidation of DCU with p-toluenesolfonyl chloride in hot pyridine.

O
p-CH 3 C6 H4 SO2 Cl
C 6H 11 NH C NH C 6H 11 C6H11 N C N C6 H 11
hot Py +
H 2O

(ii) By heating DCU with mercuric oxide (Hg2O)

Hg2O
DCU DCC + H2O

Applications:
(A) Synthesis of esters and amides:
O O
DCC
R C OH + R' OH R C O R' + DCU

Mechanism:

O O
+ – + –
H
R C OH + C6H11 N C N C6H11 R C O + C6H11 N C N C6H11
114 Oxidation
H H H O
C6H11 N C N C6H11 C6H11 N C N C6H11 + R C O R'
O Ester
O
R' OH C O O O
R' – NH2
R' O C R R C NH R'
R
Amide

O
DCC
* RCOOH + CH2N2
R CHN 2

(B) Miscellaneous Functions :

 -hydroxyester/  -hydroxy ketons on reaction with DCC undergoes dehydration as shown in the follwoing
examples.

O-tBut
HO O-tBut

DCC
O

RO R RO R
DCC
O O

HO R H R

O O

 DCC

OH

O
DCC
2RNH2 + CO2 R NH C NH R

DCC
R NH2 + CS2 R N C S

O 2
2 R
R DCC
OH C O
1 1
H R
R
Oxidation 115

+ _ _ + _ H
N C N + O C O N C N N C N

O O
+
R NH2 C O R NH C O

O DCU
H
R N C NHR R N C O
R–NH2

(C) Synthesis of organic diacyl peroxide

O O O O
DCC
Ph C O H + H O O H + H O C Ph Ph C O O C Ph + 2DCU + 2H2O

(D) Ether Formation

DCC
Ph O H + H O Et Ph O Et + H2 O + DCU
or or or
Ar SH MeOH Ar S Et

COOH
(E) Formation of Anhydrides
COOH

O O
DCC
R COOH + HOOC R' R C O C R' + DCU + H2O

DCC
HCOOH HCOOCOH
(F) Dehydroxylation of alcohols:

NH C 6H 11

R O H + C 6H 11 N C N C6 H11 R O C N C 6H 11

Pd C
H2

R H + DCU

(G) Formation of Lactone and Lactams:

DCC
  -Lactone

HOOC OH
OCH3 OCH3
O
O